Long Term Safety and Efficacy Study of Tanezumab in Subjects With Osteoarthritis of the Hip or Knee

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02528188
• Collaborator: (none)
• Enrollment: 3,021
• Locations: 507
• Arms: 3
• Actual Duration (Months): 43.3
• Patients Per Site: 6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the long-term joint safety and efficacy (pain relief) of the investigational study drug, tanezumab compared to non-steroidal anti inflammatory drugs (NSAIDs) in subjects with osteoarthritis of the hips or knees.

Condition or Disease	Intervention/Treatment	Phase
Chronic Pain; Osteoarthritis, Hip; Osteoarthritis, Knee	Drug: NSAID; Biological: Tanezumab 2.5 mg; Biological: Tanezumab 5 mg	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 3021 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND, ACTIVE-CONTROLLED, MULTICENTER STUDY OF THE LONG-TERM SAFETY AND EFFICACY OF SUBCUTANEOUS ADMINISTRATION OF TANEZUMAB IN SUBJECTS WITH OSTEOARTHRITIS OF THE HIP OR KNEE
• Actual Study Start Date: Jul 21, 2015
• Actual Primary Completion Date: Oct 5, 2018
• Actual Study Completion Date: Feb 27, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: NSAID Subcutaneous injection of placebo for tanezumab every 8 weeks plus oral NSAID (naproxen 500 mg, celecoxib 100 mg or diclofenac 75 mg) twice daily for 56 weeks	Drug: NSAID; Orally administered NSAID (naproxen 500 mg, celecoxib 100 mg or diclofenac 75 mg) twice daily for 56 weeks
Experimental: Tanezumab 2.5 mg Subcutaneous injection of tanezumab 2.5 mg every 8 weeks plus oral placebo for NSAID (naproxen, celecoxib or diclofenac ER) twice daily for 56 weeks	Biological: Tanezumab 2.5 mg; Subcutaneous injection of tanezumab 2.5 mg every 8 weeks for 56 weeks
Experimental: Tanezumab 5 mg Subcutaneous injection of tanezumab 5 mg every 8 weeks plus oral placebo for NSAID (naproxen, celecoxib or diclofenac) twice daily for 56 weeks	Biological: Tanezumab 5 mg; Subcutaneous injection of tanezumab 5 mg every 8 weeks for 56 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Adjudicated Primary Composite Joint Safety Outcome [Baseline up to Week 80]

   Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive osteoarthritis (OA) type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of joint space width (JSW) (greater than or equal to [>=] 2 millimeters [mm]) within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.

2. Observation Time-Adjusted Event Rate of Participants With Adjudicated Primary Composite Joint Safety Outcome [Baseline up to Week 80]

   Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Primary joint safety outcome included participants with adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.

3. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16 [Baseline, Week 16]

   WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions, which may not be a whole (integer) number, scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

4. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16 [Baseline, Week 16]

   WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.

5. Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16 [Baseline, Week 16]

   PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using Interactive Response Technology (IRT), where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.

Secondary Outcome Measures

1. Percentage of Participants With Adjudicated Secondary Composite Joint Safety Outcome [Baseline up to Week 80]

   Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.

2. Observation Time-Adjusted Event Rate of Participants With Adjudicated Secondary Composite Joint Safety Outcome [Baseline up to Week 80]

   Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Secondary joint safety outcome included primary osteonecrosis, rapidly progressive OA (type-2), subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.

3. Percentage of Participants With Individual Adjudicated Joint Safety Outcome [Baseline up to Week 80]

   Any participant with incidence of an adjudicated outcome of rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of JSW >=2 mm within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.

4. Observation Time-Adjusted Event Rate of Participants With Individual Adjudicated Joint Safety Outcome [Baseline up to Week 80]

   Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Individual joint safety outcome included rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.

5. Percentage of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome [Baseline up to Week 80]

   Percentage of participants with total joint replacement (hip, knee or shoulder) or adjudicated primary composite joint safety outcomes were reported. Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture.

6. Observation Time-Adjusted Event Rate of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome [Baseline up to Week 80]

   Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.

7. Change From Baseline in Medial or Lateral Joint Space Width of the Index Knee (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80 [Baseline, Weeks 56 and 80]

   Change from baseline in JSW was defined as change in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the medial and lateral tibiofemoral of knee in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral).

8. Change From Baseline in Joint Space Width of the Index Hip (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80 [Baseline, Weeks 56 and 80]

   Change from baseline in JSW was defined as narrowing in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the index hip in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.

9. Number of Participants With Progression of Osteoarthritis in the Index Knee (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80 [Weeks 56 and 80]

   Progression of OA according to Bland-Altman as defined by a decrease JSW >=1.96 times within-participant standard deviation of change in JSW. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral). Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function.

10. Number of Participants With Progression of Osteoarthritis in the Index Hip (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80 [Weeks 56 and 80]

    Progression of OA according to Bland-Altman methodology as defined by a decrease in JSW >=1.96 times within-participant standard deviation of the change in JSW in the index hip. The number of participants with progression of OA in the index hip per Bland-Altman methodology are reported. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.

11. Change From Baseline in WOMAC Pain Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56]

    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

12. Change From Baseline in WOMAC Pain Subscale at Week 64 [Baseline, Week 64]

    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

13. Change From Baseline in WOMAC Physical Function Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56]

    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.

14. Change From Baseline in WOMAC Physical Function Subscale at Week 64 [Baseline, Week 64]

    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.

15. Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56]

    PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using IRT, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.

16. Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 64 [Baseline, Week 64]

    PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using IRT, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.

17. Percentage of Participants Meeting Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 [Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64]

    Participants were considered as OMERACT-OARSI responders: if the change (improvement) from baseline to week of interest was >=50 percent and >= 2 units in either WOMAC pain subscale or physical function subscale score; if change (improvement) from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of OA. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and PGA of OA (score: 1 [very good] to 5 [very poor], higher score = worse condition). Missing data was imputed using mixed baseline/last observation carried forward (BOCF/LOCF).

18. Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 [Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64]

    Percentage of participants with reduction in WOMAC pain intensity of >= 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 compared to baseline were classified as responders to WOMAC pain subscale and are reported here. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Missing data was imputed using mixed BOCF/LOCF.

19. Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16, 24 and 56 [Baseline, Weeks 16, 24 and 56]

    WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Percentage of participants with cumulative reduction (as percent) (greater than [>] 0% ; >= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in WOMAC pain subscale from Baseline to Weeks 16, 24 and 56 were reported, participants (%) are reported more than once in categories specified. Missing data was imputed using mixed BOCF/LOCF.

20. Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction of >=30%, >=50%, >=70% and >=90% Response at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 [Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64]

    Percentage of participants with reduction in WOMAC physical function of >=(30%,50%,70%,90%) at Weeks 2,4,8,16,24,32,40,48,56 and 64 compared to baseline were classified as responders to WOMAC physical function subscale. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function:Participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee/hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.

21. Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16, 24 and 56 [Baseline, Weeks 16, 24 and 56]

    Percentage of participants with cumulative reduction (as percent) (> 0 %; >= 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and 90%; =100%) in WOMAC physical function subscale from baseline to Weeks 16, 24 and 56 were reported. WOMAC:Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function: participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale:17-item questionnaire to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), higher scores indicate extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.

22. Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 [Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64]

    PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where, 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worse condition. Percentage of participants with improvement of at least 2 points from baseline in PGA of OA were reported. Missing data was imputed using mixed BOCF/LOCF.

23. Change From Baseline in Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, 48 and 56 [Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, 48 and 56]

    Participants assessed their average pain in the index hip/knee in the past 24 hours using NRS, with a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data for Weeks 20 through 56 represents averages of the values reported during the 4-week interval up to and including the given week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.

24. Change From Baseline in Average Pain Score in the Index Joint at Week 64 [Baseline, Week 64]

    Participants assessed their average pain in the index hip/knee in the past 24 hours using NRS, with a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data represents averages of the values reported during the 4-week interval up to and including Week 64. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.

25. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.

26. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 64 [Baseline, Week 64]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.

27. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.

28. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 64 [Baseline, Week 64]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.

29. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

30. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Week 64 [Baseline, Week 64]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

31. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

32. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Week 64 [Baseline, Week 64]

    WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.

33. Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Weeks 16, 24 and 56 [Weeks 16, 24 and 56]

    WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

34. Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Week 64 [Baseline, Week 64]

    WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.

35. Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Mobility Domain [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    Number of participants with mobility domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.

36. Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Self-Care Domain [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    Number of participants with self-care domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.

37. Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Usual Activities Domain [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    Number of participants with usual activities domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.

38. Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Pain/Discomfort Domain [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    Number of participants with pain/discomfort domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.

39. Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Anxiety/ Depression Domain [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    Number of participants with anxiety/ depression domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.

40. European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score/Index Value [Baseline, Weeks 8, 16, 24, 40, 56 and 64]

    EQ-5D-5L: standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses from the five domains were used to calculate a single utility index (the Overall health utility score) where values are less than or equal to (<=) 1. The Overall health utility score for a participant with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a participant reports greater levels of problems across the five dimensions.

41. Treatment Satisfaction Questionnaire Medicine Version II (TSQM v.II) Score With Effectiveness, Side Effects, Convenience, and Overall Satisfaction Responses [Weeks 16 and 56]

    TSQM v.II is a self-administered 11-item validated scale that quantified participant's level of satisfaction with study medication (scored on a 7-point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=dissatisfied, 4=somewhat satisfied, 5=satisfied, 6=very satisfied, 7=extremely satisfied]) and dissatisfaction with side effects (3 questions scored on 5 point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=somewhat dissatisfied, 4=slightly dissatisfied, 5=not at all dissatisfied] and 1 question on 2 point scale [0 =No, 1=Yes]). Participants were asked to assess their level of satisfaction taking all things into account. The 11 questions of the TSQM were used to calculate the 4 endpoints of effectiveness, side Effects, convenience and global satisfaction, each scored on a 0-100 scale with 100 being the best level of satisfaction.

42. Patient-Reported Treatment Impact Assessment- Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving for Osteoarthritis Pain Before Enrolling? [Weeks 16 and 56]

    The mPRTI is a self-administered questionnaire containing participant's global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant's willingness to use drug again assessment. To assess current or most recent treatment, participants responded for, 1=injectable prescription medicines, 2=prescription medicines taken by mouth, 3=surgery, 4=prescription medicines and surgery and 5=no treatment. Number of participants who responded for the specified question were reported.

43. Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- Overall, do You Prefer the Drug That You Received in This Study to Previous Treatment? [Weeks 16 and 56]

    The mPRTI is a self-administered questionnaire containing participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess preference to continue using the investigational product, participants responded using IRT on a 5 point Likert scale from 1-5, where, 1= yes, I definitely prefer the drug that I am receiving now, 2= I have a slight preference for the drug that I am receiving now, 3= I have no preference either way, 4= I have a slight preference for my previous treatment, 5= No, I definitely prefer my previous treatment. Higher scores indicate lesser preference to use the investigational product. Number of participants who responded for the specified question were reported.

44. Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Willingness to Use Drug Again Assessment- Willing to Use the Same Drug That You Have Received in This Study for Your Osteoarthritis Pain? [Weeks 16 and 56]

    The mPRTI is a self-administered questionnaire containing participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess participant willingness to use drug again, participants responded using IRT on a 5 point likert scale from 1-5, where, 1= yes, I would definitely want to use the same drug again, 2= I might want to use the same drug again, 3= I am not sure, 4= I might not want to use the same drug again, 5= no, I definitely would not want to use the same drug again. Higher scores indicate lesser willingness to use the investigational product. Number of participants who responded for the specified question were reported.

45. Number of Participants Who Withdrew Due to Lack of Efficacy [Baseline up to Week 56]

    Number of participants who withdrew from treatment due to lack of efficacy have been reported here.

46. Time to Discontinuation Due to Lack of Efficacy [Baseline up to Week 56]

    Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of participant from treatment due to lack of efficacy.

47. Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    In case of inadequate pain relief, acetaminophen/paracetamol up to 3000 mg per day and up to 3 days in a week between baseline and Week 16, and 3000 mg per day and up to 7 days per week between Week 16 and 64 could be taken as rescue medication. Number of participants with any use of rescue medication during the particular study week were summarized.

48. Number of Participants Who Took Rescue Medication During Week 64 [Week 64]

    In case of inadequate pain relief, after Week 16, acetaminophen/paracetamol up to 3000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of participants with any use of rescue medication during Week 64 were summarized.

49. Number of Days of Rescue Medication Used During Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56 [Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56]

    In case of inadequate pain relief during the treatment period, acetaminophen/paracetamol up to 3000 mg per day and up to 3 days in a week between baseline and Week 16, and 3000 mg per day and up to 7 days per week between Week 16 and 64 could be taken as rescue medication. Number of days the participants used the rescue medication during the particular study weeks were summarized.

50. Number of Days of Rescue Medication Used During Week 64 [Week 64]

    In case of inadequate pain relief, after week 16, acetaminophen/paracetamol up to 3000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of days the participants used the rescue medication during Week 64 were summarized.

51. Amount of Rescue Medication Used During Weeks 2, 4, 8 and 16 [Weeks 2, 4, 8 and 16]

    In case of inadequate pain relief, acetaminophen/paracetamol up to 3000 mg per day up to 3 days in a week could be taken as rescue medication. The total dosage of acetaminophen in milligrams used during the specified week were summarized.

52. Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Visits of services directly related to OA evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner.

53. Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who visited the emergency room due to OA.

54. Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    Osteoarthritis HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of visits to the emergency room due to OA.

55. Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who were hospitalized due to OA.

56. Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of nights stayed in the hospital due to OA.

57. Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices.

58. Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who quit job due to OA.

59. Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis [Baseline, Weeks 64 and 80]

    OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was duration since quitting job due to OA.

60. Number of Participants With Categorical Change From Baseline in Lower Extremity Activity Scale (LEAS) at Weeks 4, 8, 16, 24, 56 and 80 [Baseline, Weeks 4, 8, 16, 24, 56 and 80]

    The LEAS is a self-administered scale to assess activity level in participants having total knee arthroplasty. The LEAS scale reflected four levels of lower-extremity activity (1)housebound(unable to walk or a minimal ability to walk) (2)more ordinary walking about the house (3)walking about the community (4)walking about the community as well as substantial work or exercise. It consisted of 12 questions resulting in 18-level scale that allowed participants to select a single description that most represented his or her self-perceived activity level. The final score was simply the number of the descriptor selected by the participant as being most representative of his or her activity level. The minimum possible score was 1(entirely bedbound) and the maximum possible score was 18(currently competitive athlete). Higher score indicated increased activity. Categorical changes from baseline were reported in terms of improvement (Change >0), No change and worsening (Change less than [<] 0).

61. Change From Baseline in Average Daily Minutes of Physical Activity at Weeks 16 and 56 [Baseline, Weeks 16 and 56]

    Participant activity level was assessed using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).

62. Change From Baseline in Average Daily Physical Activity Counts at Weeks 16 and 56 [Baseline, Weeks 16 and 56]

    An average daily physical activity count was measured using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).

63. Change From Baseline in Average Daily Minutes of Moderate to Vigorous Physical Activity at Weeks 16 and 56 [Baseline, Weeks 16 and 56]

    An average daily physical activity count was measured using actigraphy which was then sorted into three intensity thresholds: light (100 - less than {<1500} counts moderate (1,500 - <6500 counts), and vigorous (>=6500 counts). Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).

64. Change From Baseline in Average Daily Minutes of Bouted (Sustained) Moderate to Vigorous Physical Activity at Weeks 16 and 56 [Baseline, Weeks 16 and 56]

    An average daily physical activity count was measured using actigraphy which was then sorted into three intensity thresholds: light (100 - <1,500 counts) moderate (1,500 - <6,500 counts), and vigorous (>=6,500 counts). Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).A "bout" of moderate to vigorous activity was defined as 10 or more consecutive minutes above the moderate physical activity level threshold, with allowance for interruptions of 1 or 2 minutes below the threshold.

65. Change From Baseline in Average Daily Step Count at Weeks 16 and 56 [Baseline, Weeks 16 and 56]

    Average daily step count was measured using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).

66. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 80]

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 80 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious AEs. Clinically significant physical examination abnormalities were reported as AEs.

67. Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to Week 80]

    Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 80 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.

68. Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline [Baseline up to Week 80]

    Primary Abnormality criteria: HGB, hematocrit, RBC count <0.8* lower limit of normal(LLN); Ery. mean corpuscular volume/hemoglobin/ HGB concentration, RBCs distribution width <0.9*LLN, >1.1*upper limit of normal(ULN); platelets <0.5*LLN,>1.75*ULN; Leukocytes <0.6*LLN, >1.5*ULN; Lymphocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils,Eosinophils,Monocytes>1.2*ULN; Prothrombin time/Intl. normalized ratio>1.1*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen,creatinine,Cholesterol,triglycerides >1.3*ULN; Urate>1.2*ULN; sodium<0.95*LLN,>1.05*ULN; potassium,chloride,calcium,magnesium,bicarbonate <0.9*LLN, >1.1*ULN; phosphate<0.8*LLN, >1.2*ULN; glucose<0.6*LLN, >1.5*ULN; HGB A1C >1.3*ULN; creatine kinase>2.0*ULN, specific gravity<1.003, >1.030; pH<4.5, >8;Urine erythrocytes,Leukocytes>=20.

69. Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline [Baseline up to Week 80]

    Primary Abnormality criteria: hemoglobin; hematocrit; RBC count < 0.8*LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*ULN; platelets <0.5*LLN,>1.75*upper limit of normal (ULN); white blood cell count<0.6*LLN, >1.5*ULN; Lymphocytes, Lymphocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes <0.8*LLN, >1.2*ULN; Basophils, Eosinophils, Monocytes >1.2*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides >1.3*ULN; Urate >1.2*ULN; sodium <0.95*LLN,>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate <0.9*LLN, >1.1*ULN; phosphate <0.8*LLN, >1.2*ULN; glucose <0.6*LLN, >1.5*ULN; Hemoglobin A1C >1.3*ULN; creatine kinase >2.0*ULN; specific gravity<1.003, >1.030; Urine erythrocytes,Leukocytes>=20; Hyaline Casts>=1.

70. Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80]

    Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP).

71. Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80]

    Heart rate (pulse rate) was measured at sitting position.

72. Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 56 and 80 [Baseline, Weeks 56 and 80]

    A 12-lead ECG was recorded after participants had rested for at least 5 minutes in the supine position in a quiet environment. All standard intervals (PR, QRS, QT, QTcF, QTcB, RR intervals) were collected. ECG abnormalities included: 1) QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF): increase from baseline greater than (>) 30 millisecond (ms) or 60 ms; absolute value > 450 ms, >480 ms and > 500 ms; 2) heart rate (HR) : absolute value <=50 bpm and decrease from baseline >=20 bpm; absolute value >=120 beats per minute (bpm) and increase from baseline >=20 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS interval: absolute value >= 120 ms.

73. Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 56 and 80 [Baseline, Weeks 56 and 80]

    Heart rate was measured at sitting position.

74. Number of Participants With Confirmed Orthostatic Hypotension [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80]

    Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: For systolic BP <=150 mmHg (mean supine): Reduction in systolic BP>=20 mmHg or reduction in diastolic BP>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP >150 mmHg (mean supine): Reduction in systolic BP>=30 mmHg or reduction in diastolic BP>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.

75. Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80 [Baseline, Weeks 24, 56 and 80]

    The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total impact score was the sum of all symptom rating scores, with 0 assigned where the participant did not have the particular symptom. The range for the total impact score is 0-60 for males and 0-55 for females, higher scores indicating higher impact.

76. Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80 [Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80]

    NIS is a standardized instrument used to evaluate participant for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, from both the left and right side, where 24 items scored from 0 (normal) to 4 (paralysis), higher score indicated higher abnormality/impairment and 13 items scored from 0 (normal), 1 (decreased) and 2 (absent), higher score indicated higher impairment. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased impairment.

77. Number of Participants With Anti-Tanezumab Antibodies [Baseline, Weeks 8, 16, 32, 48, 56, 64 and 80]

    Human serum anti-drug antibody (ADA) samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A diagnosis of osteoarthritis of the index hip or knee based on American College of Rheumatology criteria with Kellgren Lawrence X ray Grade of 2 as diagnosed by the Central Reader

• Currently receiving a stable dose regimen of oral NSAID (naproxen, celecoxib, diclofenac, aceclofenac, loxoprofen, ibuprofen, meloxicam, nabumetone, sulindac or ketoprofen) as described in the protocol along with a history of insufficient pain relief from, inability to tolerate or contraindication to taking acetaminophen and, tramadol or opioid treatments. Subjects must also maintain a stabilized, protocol specified NSAID dose regimen for at least the final 2 or 3 weeks of the Screening period

• WOMAC Pain subscale score of at least 5 in the index knee or hip at Screening

• Be willing to discontinue all non study pain medications for osteoarthritis and not use prohibited pain medications throughout the duration of the study

• Female subjects of childbearing potential must agree to comply with protocol specified contraceptive requirements

Exclusion Criteria:

• Subjects exceeding protocol defined BMI or body weight limits

• History of other diseases specified in the protocol (eg, inflammatory joint diseases, crystalline diseases such as gout or pseudogout) that may involve the index joint and that could interfere with efficacy assessments

• Radiographic evidence of protocol specified bone or joint conditions in any screening radiograph as determined by the central radiology reviewer

• A history of osteonecrosis or osteoporotic fracture

• History of significant trauma or surgery to a knee, hip or shoulder within the previous year

• Planned surgical procedure during the duration of the study

• Presence of conditions (eg, fibromyaliga, radiculopathy) associated with moderate to severe pain that may confound assessments or self evaluation of osteoarthritis pain

• Signs or symptoms of carpal tunnel syndrome in the year prior to Screening

• Considered unfit for surgery based upon American Society of Anesthesiologists physical classification system for surgery grading, or subjects who would not be willing to undergo joint replacement surgery if required

• Contraindications to magnetic resonance imaging

• History of intolerance or hypersensitivity to the oral NSAID (naproxen, celecoxib or diclofenac) the subject could be randomized to receive or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of this NSAID is contraindicated

• History of intolerance or hypersensitivity to acetaminophen or any of its excipients or existence of a medical condition or use of concomitant medication for which the use of acetaminophen is contraindicated

• Use of prohibited medications without the appropriate washout period prior to Screening or Initial Pain Assessment Period

• History of cancer within 5 years of Screening, except for cutaneous basal cell or squamous cell cancer resolved by excision

• Subjects with signs and symptoms of clinically significant cardiac disease as described in the protocol

• Diagnosis of a transient ischemic attack in the 6 months prior to Screening, diagnosis of stroke with residual deficits that would preclude completion of required study activities

• History, diagnosis, or signs and symptoms of clinically significant neurological disease such as but not limited to peripheral or autonomic neuropathy

• History, diagnosis, signs or symptoms of any clinically significant psychiatric disorder

• History of known alcohol, analgesic or drug abuse within 2 years of Screening

• Previous exposure to exogenous NGF or to an anti-NGF antibody

• History of allergic or anaphylactic reaction to a therapeutic or diagnostic monoclonal antibody or IgG fusion protein

• Poorly controlled hypertension as defined in the protocol or taking an antihypertensive that has not been stable for at least 1 month prior to Screening

• Evidence of protocol defined orthostatic hypotension at Screening

• Disqualifying score on the Survey of Autonomic Symptoms questionnaire at Screening

• Screening AST, ALT, serum creatinine or HbA1c values that exceed protocol defined limits

• Presence of drugs of abuse in screening urine toxicology panel

• Positive hepatitis B, hepatitis C or HIV test results indicative of current infection

• Participation in other investigational drug studies within protocol defined time limits

• Pregnant, breastfeeding or female subjects of childbearing potential who are unwilling or unable to follow protocol required contraceptive requirements

• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the judgment of the investigator, would make the subject inappropriate for entry into this study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Alabama Research	Birmingham	Alabama	United States	35209
2	Achieve Clinical Research, LLC	Birmingham	Alabama	United States	35216
3	Alabama Clinical Therapeutics, LLC	Birmingham	Alabama	United States	35235
4	Alabama Orthopaedic Surgeons	Birmingham	Alabama	United States	35235
5	Rheumatology Associates of North Alabama, PC	Huntsville	Alabama	United States	35801
6	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
7	Ferguson Family Medicine	Mesa	Arizona	United States	85215
8	Arizona Arthritis & Rheumatology Associates, P.C.	Phoenix	Arizona	United States	85032
9	Arizona Research Center	Phoenix	Arizona	United States	85053
10	Valley Pain Consultants	Scottsdale	Arizona	United States	85254
11	Clinical Research Consortium	Tempe	Arizona	United States	85283
12	Noble Clinical Research, LLC	Tucson	Arizona	United States	85704
13	Quality of Life Medical & Research Centers, LLC	Tucson	Arizona	United States	85712
14	Tucson Orthopaedic Institute - Research Center	Tucson	Arizona	United States	85712
15	CHI St. Vincent Medical Group Hot Springs	Hot Springs	Arkansas	United States	71913
16	Chrystal Johnson	Little Rock	Arkansas	United States	72205
17	KLR Business Group, Inc., dba Arkansas Clinical Research	Little Rock	Arkansas	United States	72205
18	Larry Watkins, MD	Little Rock	Arkansas	United States	72205
19	Lynn Institute of the Ozarks	Little Rock	Arkansas	United States	72205
20	Orange County Research Institute	Anaheim	California	United States	92801
21	Advanced Research Center	Anaheim	California	United States	92805
22	CITrials	Bellflower	California	United States	90706
23	Osteoporosis Medical Center	Beverly Hills	California	United States	90211
24	Hope Clinical Research	Canoga Park	California	United States	91303
25	Med Center	Carmichael	California	United States	95608
26	Core Healthcare Group	Cerritos	California	United States	90703
27	Pleitez Medical Clinic	Covina	California	United States	91723
28	Triwest Research Associates, LLC	El Cajon	California	United States	92020
29	T. Joseph Raoof MD, INC/Encino Research Center	Encino	California	United States	91436
30	San Diego Imaging Escondido	Escondido	California	United States	92029
31	Med Investigations, Inc.	Fair Oaks	California	United States	95628
32	Research Center of Fresno, Inc.	Fresno	California	United States	93702
33	Neuro-Pain Medical Center	Fresno	California	United States	93710
34	Collaborative Neuroscience Network, LLC.	Garden Grove	California	United States	92845
35	Allied Clinical Research	Gold River	California	United States	95670
36	HealthCare Partners Clinical Research, LLC.	Huntington Beach	California	United States	92646
37	Marvel Clinical Research LLC	Huntington Beach	California	United States	92647
38	BioSolutions Clinical Research Center	La Mesa	California	United States	91941
39	eStudySite	La Mesa	California	United States	91942
40	Arthritis & Osteoporosis Medical Center	La Palma	California	United States	90723
41	Center For United Research, Inc.	Lakewood	California	United States	90805
42	Collaborative Neuroscience Network, LLC.	Long Beach	California	United States	90806
43	Aeon Research, Inc.	Los Angeles	California	United States	90010
44	American Institute of Research	Los Angeles	California	United States	90017
45	InterMed Medical Group	Los Angeles	California	United States	90017
46	IMD Medical Group	Los Angeles	California	United States	90020
47	Catalina Research Institute, LLC	Montclair	California	United States	91763
48	Providence Clinical Research	North Hollywood	California	United States	91606
49	Renaissance Imaging Medical Associates, Inc	Northridge	California	United States	91328
50	NRC Research Institute	Orange	California	United States	92868
51	Advances in Medicine	Palm Desert	California	United States	92260
52	Probe Clinical Research Corporation	Riverside	California	United States	92501
53	University of California, Davis Health System	Sacramento	California	United States	95817
54	University of California, Davis Medical Center	Sacramento	California	United States	95817
55	Clinical Trials Research	Sacramento	California	United States	95821
56	Northern California Research	Sacramento	California	United States	95821
57	Center for Clinical Trials of Sacramento, Inc.	Sacramento	California	United States	95823
58	Artemis Institute for Clinical Research	San Diego	California	United States	92103
59	San Diego Imaging, Kearny Mesa	San Diego	California	United States	92123
60	Sharp and Children's MRI Center, LLC	San Diego	California	United States	92123
61	Artemis Institute for Clinical Research	San Marcos	California	United States	92078
62	CITrials	Santa Ana	California	United States	92705
63	Syrentis Clinical Research	Santa Ana	California	United States	92705
64	Shariar Cohen, MD Corp.	Thousand Oaks	California	United States	91360
65	Westlake Medical Research	Thousand Oaks	California	United States	91360
66	Bayview Research Group	Valley Village	California	United States	91607
67	Renaissance Imaging Medical Associates, Inc	Van Nuys	California	United States	91405
68	Buhay & Maglunog MDS	West Covina	California	United States	91790
69	Prohealth Advanced Imaging	West Hills	California	United States	91303
70	Advanced Rx Clinical Research Group, Inc	Westminster	California	United States	92683
71	Medvin Clinical Research	Whittier	California	United States	90602
72	Elite Clinical Trials	Wildomar	California	United States	92595
73	Mountain View Clinical Research, Inc.	Denver	Colorado	United States	80209
74	Mountain View Clinical Research, Inc	Denver	Colorado	United States	80209
75	New England Research Associates, LLC	Bridgeport	Connecticut	United States	06606
76	Clinical Research Center of CT	Danbury	Connecticut	United States	06810
77	Stamford Therapeutics Consortium	Stamford	Connecticut	United States	06905
78	Delaware Arthritis	Lewes	Delaware	United States	19958
79	Javed Rheumatology Associates, Inc.	Newark	Delaware	United States	19713
80	JEM Research Institute	Atlantis	Florida	United States	33462
81	AARDS Research, Inc.	Aventura	Florida	United States	33180
82	RASF-Clinical Research, Inc	Boca Raton	Florida	United States	33486
83	Orthopedic Research Institute	Boynton Beach	Florida	United States	33472
84	Meridien Research	Brooksville	Florida	United States	34601
85	Orthopaedic Associates of West Florida	Clearwater	Florida	United States	33756
86	Tampa Bay Medical Research, Inc	Clearwater	Florida	United States	33761
87	Midland Florida Clinical Research Center, LLC	DeLand	Florida	United States	32720
88	S&W Clinical Research	Fort Lauderdale	Florida	United States	33306
89	Centre for Rheumatology, Immunology and Arthritis	Fort Lauderdale	Florida	United States	33309
90	Clinical Physiology Associates	Fort Myers	Florida	United States	33912
91	IMA	Fort Myers	Florida	United States	33912
92	SIMEDHealth, LLC	Gainesville	Florida	United States	32607
93	South Florida Clinical Trials	Hialeah	Florida	United States	33016
94	Pines Clinical Research Inc.	Hollywood	Florida	United States	33024
95	Jacksonville Center for Clinical Research	Jacksonville	Florida	United States	32216
96	Care Partners Clinical Research	Jacksonville	Florida	United States	32218
97	Clinical Neuroscience Solutions, Inc.	Jacksonville	Florida	United States	32256
98	Columbus Clinical Services LLC	Miami	Florida	United States	33125
99	Pharmax Research Clinic, Inc.	Miami	Florida	United States	33126
100	Clintex Research Group	Miami	Florida	United States	33135
101	Center for Arthritis and Rheumatic Diseases	Miami	Florida	United States	33173
102	Larkin Imaging Center	Miami	Florida	United States	33173
103	New Horizon Research Center	Miami	Florida	United States	33175
104	International Research Associates, LLC	Miami	Florida	United States	33183
105	M&M Medical Center, Inc.	Miami	Florida	United States	33185
106	Quality Research & Medical Center LLC	Miami	Florida	United States	33186
107	Renstar Medical Research	Ocala	Florida	United States	34470
108	American Family Medical	Ocala	Florida	United States	34471
109	Sensible Healthcare, LLC.	Ocoee	Florida	United States	34761
110	Journey Research, Inc.	Oldsmar	Florida	United States	34677
111	Sunshine Research Center	Opa-locka	Florida	United States	33054
112	Compass Research, LLC	Orlando	Florida	United States	32806
113	Rheumatology Associates of Central Florida, P.A.	Orlando	Florida	United States	32806
114	Omega Research Consultants, LLC	Orlando	Florida	United States	32810
115	Oviedo Medical Research, LLC	Oviedo	Florida	United States	32765
116	Pensacola Research Consultants, Inc., d.b.a. Avanza Medical Research Center	Pensacola	Florida	United States	32503
117	Sacred Heart Orthopedics	Pensacola	Florida	United States	32503
118	Orthopaedic Center of South Florida	Plantation	Florida	United States	33324
119	St. Johns Center for Clinical Research	Ponte Vedra	Florida	United States	32081
120	Progressive Medical Research	Port Orange	Florida	United States	32127
121	Accord Clinical Research, LLC	Port Orange	Florida	United States	32129
122	Meridien Research	Saint Petersburg	Florida	United States	33709
123	Gulfcoast Research Institute, LLC	Sarasota	Florida	United States	34232
124	Kennedy White Orthopaedic Center	Sarasota	Florida	United States	34232
125	Precision Clinical Research, LLC.	Sunrise	Florida	United States	33351
126	Phoenix Clinical Research, LLC.	Tamarac	Florida	United States	33321
127	Clinical Research of West Florida, Inc.	Tampa	Florida	United States	33603
128	Stedman Clinical Trials	Tampa	Florida	United States	33613
129	BayCare Medical Group, Inc	Tampa	Florida	United States	33614
130	Compass Research North LLC	The Villages	Florida	United States	32162
131	Palm Beach Research Center	West Palm Beach	Florida	United States	33409
132	Atlanta Center for Medical Research	Atlanta	Georgia	United States	30331
133	Perimeter Institute for Clinical Research, Inc. DBA:/PICR Clinic	Atlanta	Georgia	United States	30338
134	Masters of Clinical Research, Inc.	Augusta	Georgia	United States	30909
135	River Birch Research Alliance, LLC	Blue Ridge	Georgia	United States	30513
136	Arthritis Center of North Georgia	Gainesville	Georgia	United States	30501
137	Center for Advanced Research & Education	Gainesville	Georgia	United States	30501
138	Drug Studies America	Marietta	Georgia	United States	30060
139	Better Health Clinical Research, Inc.	Newnan	Georgia	United States	30265
140	Atlanta Orthopaedic Institute, LLC	Stockbridge	Georgia	United States	30281
141	Herman Clinical Research, LLC	Suwanee	Georgia	United States	30024
142	North Georgia Clinical Research	Woodstock	Georgia	United States	30189
143	North Georgia Internal Medicine	Woodstock	Georgia	United States	30189
144	East-West Medical Research Institute	Honolulu	Hawaii	United States	96814
145	Idaho Sports Medicine Institute	Boise	Idaho	United States	83706
146	Injury Care Research, LLC	Boise	Idaho	United States	83713
147	Institute Of Arthritis Research	Idaho Falls	Idaho	United States	83404
148	Advanced Clinical Research	Meridian	Idaho	United States	83642
149	Medex Healthcare Research, Inc.	Chicago	Illinois	United States	60602
150	Chicago Clinical Research Institute Inc.	Chicago	Illinois	United States	60607
151	Northwestern Memorial Hospital-Arkes Pavilion, Diagnostic Testing Center	Chicago	Illinois	United States	60611
152	Northwestern University Feinberg School of Medicine	Chicago	Illinois	United States	60611
153	Rush University Medical Center	Chicago	Illinois	United States	60612
154	Great Lakes Clinical Trials	Chicago	Illinois	United States	60640
155	Affinity Clinical Research Institute	Oak Lawn	Illinois	United States	60453
156	Southwest Center for Healthy Joints, S.C.	Oak Lawn	Illinois	United States	60453
157	Methodist Research Administration Office	Peoria	Illinois	United States	61602
158	UnityPoint Clinic Rheumatology	Peoria	Illinois	United States	61602
159	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
160	OrthoIllinois	Rockford	Illinois	United States	61114
161	Quest Diagnostics	Rockford	Illinois	United States	61114
162	MediSphere Medical Research Center, LLC	Evansville	Indiana	United States	47714
163	Buynak Clinical Research, P.C.	Valparaiso	Indiana	United States	46383
164	Mid-America Physiatrists, P.A.	Overland Park	Kansas	United States	66210
165	Phoenix Medical Research, Inc.	Prairie Village	Kansas	United States	66208
166	Professional Research Network of Kansas, LLC	Wichita	Kansas	United States	67205-1138
167	Heartland Research Associates, LLC	Wichita	Kansas	United States	67207
168	Otrimed Corporation	Edgewood	Kentucky	United States	41017
169	Central Kentucky Research Associates, Inc.	Lexington	Kentucky	United States	40509
170	Baton Rouge General Medical Center-Internal Medicine Clinic	Baton Rouge	Louisiana	United States	70806
171	Baton Rouge General Medical Center-Midcity	Baton Rouge	Louisiana	United States	70806
172	Baton Rouge General Medical Center-Bluebonnet	Baton Rouge	Louisiana	United States	70809
173	Baton Rouge General Medical Center-Clinical Trials Office	Baton Rouge	Louisiana	United States	70809
174	Centex Studies, Inc.	Lake Charles	Louisiana	United States	70601
175	Klein & Associates, M.D., P.A.	Cumberland	Maryland	United States	21502
176	Arthritis Treatment Center	Frederick	Maryland	United States	21702
177	Klein & Associates, M.D., P.A.	Hagerstown	Maryland	United States	21740
178	The Center for Rheumatology and Bone Research	Wheaton	Maryland	United States	20902
179	Beacon Clinical Research, LLC	Quincy	Massachusetts	United States	02169
180	MedVadis Research Corporation	Watertown	Massachusetts	United States	02472
181	Great Lakes Research Group, Incorporated	Bay City	Michigan	United States	48706
182	Onyx Clinical Research	Caro	Michigan	United States	48723
183	Orthopaedic Associates of Michigan, PC	Grand Rapids	Michigan	United States	49525
184	June D.O. PC	Lansing	Michigan	United States	48910
185	Great Lakes Research Group	Pinconning	Michigan	United States	48650
186	Michigan Orthopaedic Spine Surgeons	Rochester Hills	Michigan	United States	48307
187	Medical Research Associates Inc.	Traverse City	Michigan	United States	49686
188	Oakland Medical Research Center	Troy	Michigan	United States	48085
189	Olive Branch Family Medical Center	Olive Branch	Mississippi	United States	38654
190	Landmark Internal Medicine	Southaven	Mississippi	United States	38671
191	University of Missouri Health Care-Investigational Pharmacy	Columbia	Missouri	United States	65212
192	University of Missouri Health Care	Columbia	Missouri	United States	65212
193	University of Missouri School of Medicine- Clinical Research Center	Columbia	Missouri	United States	65212
194	Advance Clinical Research, Inc.	Saint Louis	Missouri	United States	63109
195	Medex Healthcare Research, Inc.	Saint Louis	Missouri	United States	63117
196	Physician Research Collaboration, LLC	Lincoln	Nebraska	United States	68516
197	Affiliated Clinical Research, Inc.	Las Vegas	Nevada	United States	89106
198	Impact Clinical Trials	Las Vegas	Nevada	United States	89106
199	Office of Stephen H. Miller, MD	Las Vegas	Nevada	United States	89117
200	Clinical Research Consortium	Las Vegas	Nevada	United States	89119
201	Office of Robert P. Kaplan, DO	Las Vegas	Nevada	United States	89119
202	Advanced Biomedical Research of America	Las Vegas	Nevada	United States	89123
203	G. Timothy Kelly, MD	Las Vegas	Nevada	United States	89128
204	ActivMed Practices & Research, Inc.	Portsmouth	New Hampshire	United States	03801
205	Ocean Rheumatology, PA	Toms River	New Jersey	United States	08755
206	Premier Research	Trenton	New Jersey	United States	08611
207	Arthritis, Rheumatic and Back Disease Associates, PA	Voorhees	New Jersey	United States	08043
208	Albuquerque Clinical Trials, Inc.	Albuquerque	New Mexico	United States	87102
209	New Mexico Clinical Research & Osteoporosis Center, Inc.	Albuquerque	New Mexico	United States	87106
210	Lovelace Scientific Resources Inc.	Albuquerque	New Mexico	United States	87108
211	NYU Langone Ambulatory Care Brooklyn Heights	Brooklyn	New York	United States	11201
212	Drug Trials Brooklyn	Brooklyn	New York	United States	11230
213	SPRI Clinical Trials, LLC	Brooklyn	New York	United States	11235
214	Drug Trials America	Hartsdale	New York	United States	10530
215	NYU Langone Arena Oncology, Laura and Issac Perlmutter Cancer Center, Infusion Center	Lake Success	New York	United States	11042
216	NYU Langone Arena Oncology, Laura and Issac Perlmutter Cancer Center	Lake Success	New York	United States	11042
217	NYU Langone Rheumatology Associates Long Island	Lake Success	New York	United States	11042
218	Lenox Hill Radiology	New York	New York	United States	10016
219	Manhattan Medical Research Practice PLLC	New York	New York	United States	10016
220	The Medical Research Network, LLC	New York	New York	United States	10128
221	AAIR Research Center	Rochester	New York	United States	14618
222	Upstate Clinical Research Associates, LLC	Williamsville	New York	United States	14221
223	Northstate Clinical Research, PLLC	Lenoir	North Carolina	United States	28645
224	Wake Internal Medicine Consultants, Inc	Raleigh	North Carolina	United States	27612
225	Wake Research Associates, LLC	Raleigh	North Carolina	United States	27612
226	The Center for Clinical Research	Winston-Salem	North Carolina	United States	27103
227	Lillestol Research, LLC	Fargo	North Dakota	United States	58103
228	Plains Clinical Research Center, LLC	Fargo	North Dakota	United States	58104
229	Valley Medical Research/Valley Medical Primary Care	Centerville	Ohio	United States	45459
230	Hightop Medical Research Center	Cincinnati	Ohio	United States	45224
231	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
232	CTI Clinical Research Center	Cincinnati	Ohio	United States	45255
233	Aventiv Research Inc.	Columbus	Ohio	United States	43213
234	Remington-Davis, Incorporated	Columbus	Ohio	United States	43215
235	Optimed Research LTD	Columbus	Ohio	United States	43235
236	Dayton Clinical Research	Dayton	Ohio	United States	45406
237	PriMed Clinical Research	Dayton	Ohio	United States	45419
238	Kettering Medical Center	Kettering	Ohio	United States	45429
239	Springboro Health Center	Springboro	Ohio	United States	45066
240	AC Clinical Research	Tiffin	Ohio	United States	44883
241	Glendale Medical Center	Toledo	Ohio	United States	43614
242	Bone Joint & Spine Surgeons, Inc.	Toledo	Ohio	United States	43623
243	Health Research of Oklahoma	Oklahoma City	Oklahoma	United States	73103
244	Lynn Health Science Institute	Oklahoma City	Oklahoma	United States	73112
245	University Orthopedics Center	Altoona	Pennsylvania	United States	16602
246	Heritage Valley Medical Group, Inc.	Beaver	Pennsylvania	United States	15009
247	Brandywine Clinical Research	Downingtown	Pennsylvania	United States	19335
248	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
249	The Clinical Trial Center LLC	Jenkintown	Pennsylvania	United States	19046
250	Founders Research Corporation	Philadelphia	Pennsylvania	United States	19114
251	The Arthritis Group	Philadelphia	Pennsylvania	United States	19152
252	Clinical Research Center of Reading, LLC	Wyomissing	Pennsylvania	United States	19610
253	Main Street Physician's Care - Waterway	Little River	South Carolina	United States	29566
254	Main Street Physician's Care - Loris	Loris	South Carolina	United States	29569
255	North Myrtle Beach Family Practice	North Myrtle Beach	South Carolina	United States	29582
256	Clinical Research Solutions	Jackson	Tennessee	United States	38305
257	Physicians Quality Care	Jackson	Tennessee	United States	38305
258	PMG Research, Inc. d/b/a PMG Research of Knoxville	Jefferson City	Tennessee	United States	37760
259	PCET Research Center, LLC	Knoxville	Tennessee	United States	37909
260	Diagnostic Imaging PC	Memphis	Tennessee	United States	38119
261	ARC Clinical Research at Wilson Parke	Austin	Texas	United States	78726
262	Tekton Research, Inc.	Austin	Texas	United States	78745
263	Urgent Care MD's	Baytown	Texas	United States	77521
264	Texas Orthopedic Specialists, PLLC	Bedford	Texas	United States	76021
265	Galenos Research	Dallas	Texas	United States	75251
266	Abigail R. Neiman, MD, PA	Houston	Texas	United States	77024
267	Advances in Health	Houston	Texas	United States	77030
268	Mercury Clinical Research, Inc.	Houston	Texas	United States	77036
269	Centex Studies, Inc.	Houston	Texas	United States	77058
270	Memorial Pulmonology	Houston	Texas	United States	77079
271	BI Research Center	Houston	Texas	United States	77084
272	Clinical Investigations of Texas	Plano	Texas	United States	75075
273	ClinRX Research	Richardson	Texas	United States	75080
274	Quality Research, Inc.	San Antonio	Texas	United States	78209
275	Lee Medical Associates PA	San Antonio	Texas	United States	78213
276	Progressive Clinical Research, PA	San Antonio	Texas	United States	78213
277	Sun Research Institute	San Antonio	Texas	United States	78215
278	Panacea Clinical Research	San Antonio	Texas	United States	78228
279	Accurate Clinical Research Inc.	San Antonio	Texas	United States	78229
280	Diagnostics Research Group	San Antonio	Texas	United States	78229
281	Victorium Clinical Research	San Antonio	Texas	United States	78230
282	DCT-Stone Oak, LLC dba Discovery Clinical Trials	San Antonio	Texas	United States	78258
283	South Texas Radiology Imaging Centers	San Antonio	Texas	United States	78258
284	Envision Imaging	Southlake	Texas	United States	76092
285	Oakbend Medical Center	Sugar Land	Texas	United States	77479
286	ClinPoint Trials	Waxahachie	Texas	United States	75165
287	Mercury Clinical Research	Webester	Texas	United States	77598
288	Clinics of North Texas	Wichita Falls	Texas	United States	76302
289	Grayline Clinical Drug Trials	Wichita Falls	Texas	United States	76309
290	Granger Medical Clinic-Riverton	Riverton	Utah	United States	84065
291	Millennium Clinical Trials, LLC	Arlington	Virginia	United States	22207
292	Charlottesville Medical Research Center, LLC	Charlottesville	Virginia	United States	22911
293	Millennium Clinical Trials	Fairfax	Virginia	United States	22031
294	National Clinical Research-Norfolk, Inc.	Norfolk	Virginia	United States	23502
295	Northwest Clinical Research Center	Bellevue	Washington	United States	98007
296	Optimed Research, LTD	Bellingham	Washington	United States	98225
297	Swedish Medical Center Investigational Drug Services Pharmacy	Seattle	Washington	United States	98104
298	Seattle Rheumatology Associates	Seattle	Washington	United States	98122
299	Swedish Medical Center	Seattle	Washington	United States	98122
300	Genesis Research Services	Broadmeadow	New South Wales	Australia	2292
301	Hunter Imaging Group	Cardiff	New South Wales	Australia	2285
302	Optimus Clinical Research Pty Ltd	Kogarah	New South Wales	Australia	2217
303	Southern Radiology	Miranda	New South Wales	Australia	2228
304	Royal Hospital for Women	Randwick	New South Wales	Australia	2031
305	Castlereagh Imaging	St Leonards	New South Wales	Australia	2065
306	Royal North Shore Hospital	St Leonards	New South Wales	Australia	2065
307	Australian Clinical Research Network	Sydney	New South Wales	Australia	2035
308	Spectrum Medical Imaging	Sydney	New South Wales	Australia	2035
309	AusTrials Pty Ltd	Sherwood	Queensland	Australia	4075
310	CMAX Clinical Research Pty Ltd	Adelaide	South Australia	Australia	5000
311	Royal Adelaide Hospital Pharmacy	Adelaide	South Australia	Australia	5000
312	Bensons Radiology	North Adelaide	South Australia	Australia	5006
313	Emeritus Research	Camberwell	Victoria	Australia	3124
314	Capital Radiology-Malvern	Melbourne	Victoria	Australia	3144
315	Capital Radiology-Clayton	Melbourne	Victoria	Australia	3168
316	SKG Radiology Hollywood	Nedlands	Western Australia	Australia	6009
317	RK Will Pty Ltd	Victoria Park	Western Australia	Australia	6100
318	CMIP-Centro Mineiro de Pesquisa LTDA	Juiz de Fora	Minas Gerais	Brazil	36010-570
319	CCBR - Centro de Pesquisas e Analises Clinicas LTDA	Rio De Janeiro	RJ	Brazil	22271-100
320	CEPIC - Centro Paulista de Investigacao Clinica e Servicos Medicos Ltda	Sao Paulo	SP	Brazil	04266-010
321	Diagnostic Consultative Center "Sveti Georgi" EOOD	Plovdiv		Bulgaria	4000
322	Medical Center "Health for all" - EOOD	Plovdiv		Bulgaria	4000
323	UMHAT Kaspela - EOOD Rheumatology Clinic	Plovdiv		Bulgaria	4001
324	UMHAT Kaspela - EOOD	Plovdiv		Bulgaria	4001
325	"Medical Center Teodora" EOOD	Ruse		Bulgaria	7012
326	Diagnostic Consultative Center 17 Sofia EOOD	Sofia		Bulgaria	1505
327	UMHAT Sveti Ivan Rilski- EAD	Sofia		Bulgaria	1612
328	UMHAT "Sofiamed" OOD, Block 2	Sofia		Bulgaria	1750
329	"Medical Center- Dr. Hayvazov" EOOD	Sofia		Bulgaria	1784
330	Centro Integral de Reumatologia Reumalab S.A.S.	Medellin	Antioquia	Colombia	05001000
331	Centro de Investigacion en Reumatologia y Especialidades Medicas SAS CIREEM SAS	Bogota	Bogota DC	Colombia	110221
332	Medicinski centar Kuna&Peric	Zagreb		Croatia	10000
333	National Hospital Organization Toyohashi Medical Center	Toyohashi	Aichi	Japan	440-8510
334	Funabashi Municipal Medical Center	Funabashi	Chiba	Japan	273-8588
335	Matsudo City General Hospital	Matsudo	Chiba	Japan	270-2296
336	Kanbara Clinic	Kitakyushu	Fukuoka	Japan	806-0026
337	Hidaka Orthopedic Hospital	Kurume	Fukuoka	Japan	830-0053
338	Obase Hospital	Miyako-gun	Fukuoka	Japan	800-0344
339	Himeno Hospital	Yamegun	Fukuoka	Japan	834-0115
340	Ikeda Kinen Hospital	Sukagawa	Fukushima	Japan	962-0001
341	Zenshukai Hospital	Maebashi	Gunma	Japan	379-2115
342	Mazda Hospital	Aki-gun	Hiroshima	Japan	735-8585
343	Medical Corporation Okimoto Clinic	Kure	Hiroshima	Japan	734-0304
344	Medical Corporation Emu Emukai, Matterhorn Rehabilitation Hospital	Kure	Hiroshima	Japan	737-0046
345	Takahashi Orthopedics Clinic	Chitose	Hokkaido	Japan	066-0062
346	Obihiro Orthopaedic Hospital	Obihiro	Hokkaido	Japan	080-0802
347	Okubo Hospital	Akashi	Hyogo	Japan	674-0051
348	Omuro Orthopedic Clinic	Himeji	Hyogo	Japan	670-0976
349	Medical corporate corporation hoshikai Onishi medical clinic	Kako-gun	Hyogo	Japan	675-1115
350	Kobe Red Cross Hospital	Kobe	Hyogo	Japan	651-0073
351	Mito Saiseikai General Hospital	Mito	Ibaraki	Japan	311-4198
352	National Hospital Organization Kanazawa Medical Center	Kanazawa	Ishikawa	Japan	920-8650
353	Kokan Clinic	Kawasaki	Kanagawa	Japan	210-0852
354	Misugikai Medical Corporation Otokoyama Hospital	Yawata	Kyoto	Japan	614-8366
355	Nakajo Orthopedic Clinic	Sendai	Miyagi	Japan	983-0862
356	Marunouchi Hospital	Matsumoto	Nagano	Japan	390-8601
357	Oita University Hospital	Yufu	Oita	Japan	879-5593
358	Sobajima Clinic/Orthopedics	Higashiosaka	Osaka	Japan	577-0011
359	Rinku General Medical Center	Izumisano	Osaka	Japan	598-8577
360	Kishiwada Tokushukai Hospital	Kishiwada	Osaka	Japan	596-8522
361	Social Welfare Organization Saiseikai Imperial Gift Foundation,Inc. Osaka Saiseikai Nakatsu Hospital	Osaka-shi	Osaka	Japan	530-0012
362	Osaka University Hospital	Suita	Osaka	Japan	565-0871
363	Shimane University Hospital	Izumo	Shimane	Japan	693-8501
364	Fujieda Municipal General Hospital	Fujieda	Shizuoka	Japan	426-8677
365	JA Shizuoka Kohseiren Enshu Hospital	Hamamatsu	Shizuoka	Japan	430-0929
366	Japanese Red Cross Hamamatsu Hospital	Hamamatsu	Shizuoka	Japan	434-8533
367	Sonodakai Joint Replacement Center Hospital	Adachi-ku	Tokyo	Japan	121-0064
368	Medical Plaza Edogawa	Edogawa-ku	Tokyo	Japan	133-0052
369	Sato Orthopaedic Clinic	Edogawa-ku	Tokyo	Japan	134-0084
370	Fussa Hospital	Fussa	Tokyo	Japan	197-8511
371	Jukoukai hospital	Koto-ku	Tokyo	Japan	136-0073
372	Kitasato University Kitasato Institute Hospital	Minato-ku	Tokyo	Japan	108-8642
373	Tamagawa Hospital	Setagaya-ku	Tokyo	Japan	158-0095
374	Kohno Clinical Medicine Research Institute Daisan Kitashinagawa Hospital	Shinagawa-ku	Tokyo	Japan	140-0001
375	Ohimachi Orthopaedic Clinic	Shinagawa-ku	Tokyo	Japan	140-0014
376	Japan Organization of Occupational Health and Safety Sanin Rosai Hospital	Yonago	Tottori	Japan	683-8605
377	National Hospital Organization Chiba Medical Center	Chiba		Japan	260-8606
378	Chihaya Hospital	Fukuoka		Japan	813-8501
379	Kuroda Orthopedic Hospital	Fukuoka		Japan	814-0165
380	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital	Hiroshima		Japan	730-8619
381	Hiroshima Prefectural Hospital	Hiroshima		Japan	734-8530
382	Kumamoto Orthopaedic Hospital	Kumamoto		Japan	862-0976
383	Nagayoshi General Hospital	Osaka		Japan	547-0016
384	Iwasaki Orthopedic Surgery	Saitama		Japan	330-0056
385	Saitama Municipal Hospital	Saitama		Japan	336-8522
386	Daegu Catholic University Medical Center	Daegu		Korea, Republic of	42472
387	Department of Radiology	Daegu		Korea, Republic of	42472
388	Division of Rheumatology, Department of Internal Medicine, Daegu Catholic University Medical Center	Daegu		Korea, Republic of	42472
389	Chungnam National University Hospital	Daejeon		Korea, Republic of	35015
390	Clinical Trial Center Pharmacy	Daejeon		Korea, Republic of	35015
391	Department of Radiology	Daejeon		Korea, Republic of	35015
392	Chonnam National University Hospital	Gwangju		Korea, Republic of	61469
393	Department of Radiology	Gwangju		Korea, Republic of	61469
394	Pharmacy of Clinical Trial Center	Gwangju		Korea, Republic of	61469
395	Clinical Trial Pharmacy	Seoul		Korea, Republic of	02841
396	Department of Radiology	Seoul		Korea, Republic of	02841
397	Korea University Anam Hospital	Seoul		Korea, Republic of	02841
398	Clinical Trials Center Pharmacy	Seoul		Korea, Republic of	03080
399	Seoul National University Hospital	Seoul		Korea, Republic of	03080
400	Clinical Trial Center Pharmacy	Seoul		Korea, Republic of	03722
401	Department of Radiology	Seoul		Korea, Republic of	03722
402	Yonsei University Health System, Severance Hospital	Seoul		Korea, Republic of	03722
403	Clinical Research Pharmacy	Seoul		Korea, Republic of	05030
404	Department of Clinical Research Pharmacy, Konkuk University Medical Center	Seoul		Korea, Republic of	05030
405	Department of Radiology	Seoul		Korea, Republic of	05030
406	Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center	Seoul		Korea, Republic of	05030
407	Konkuk University Medical Center	Seoul		Korea, Republic of	05030
408	Clinical Trial Center Pharmacy	Seoul		Korea, Republic of	06351
409	Department of Orthopedic Surgery, Samsung Medical Center	Seoul		Korea, Republic of	06351
410	Clinical Trial Pharmacy	Seoul		Korea, Republic of	06591
411	Department of Radiology	Seoul		Korea, Republic of	06591
412	The Catholic University of Korea Seoul St. Mary's Hospital	Seoul		Korea, Republic of	06591
413	Clinical Research Pharmacy, SMG SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
414	Department of Clinical Research Pharmacy, SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
415	Department of Radiology	Seoul		Korea, Republic of	07061
416	SMG-SNU Boramae Medical Center	Seoul		Korea, Republic of	07061
417	Department of Radiology	Seoul		Korea, Republic of	07985
418	Ewha Womans University Mokdong Hospital	Seoul		Korea, Republic of	07985
419	Clinical Trial Pharmacy	Yangcheon-gu, Seoul		Korea, Republic of	07985
420	Saules seimos medicinos centras	Kaunas		Lithuania	LT-49449
421	Klaipeda University Hospital	Klaipeda		Lithuania	LT-92288
422	Republican Siauliai Hospital	Siauliai		Lithuania	LT-76231
423	Centro Hospitalario Mac, S.A. de C.V.	Guadajara	Jalisco	Mexico	45050
424	Consultorio Medico del Dr. Federico Galvan Villegas	Guadalajara	Jalisco	Mexico	45040
425	Lakeland Clinical Trials	Rotorua	BOP	New Zealand	3010
426	Otago Radiology	Dunedin	Otago	New Zealand	9010
427	RMC Medical Research Ltd	Dunedin	Otago	New Zealand	9012
428	South Pacific Clinical Trials	Auckland		New Zealand	0610
429	TRG Imaging Lincoln Road	Auckland		New Zealand	0610
430	Auckland Bone Density Ltd	Auckland		New Zealand	0612
431	North Shore Hospital, Waitemata District Health Board	Auckland		New Zealand	0622
432	Star Unit, North Shore Hospital, Waitemata District Health Board	Auckland		New Zealand	0622
433	The Radiology Group	Auckland		New Zealand	0622
434	Southern Clinical Trials- Waitemata Ltd	Auckland		New Zealand	0626
435	Auckland Bone Density	Auckland		New Zealand	0632
436	Optimal Clinical Trials	Auckland		New Zealand	1010
437	Auckland Radiology Parnell Branch	Auckland		New Zealand	1052
438	Southern Clinical Trials Ltd	Christchurch		New Zealand	8013
439	Collingwood Street Pharmacy	Nelson		New Zealand	7010
440	Nelson Radiology	Nelson		New Zealand	7010
441	Porter Rheumatology Ltd	Nelson		New Zealand	7010
442	Bay Radiology	Tauranga		New Zealand	3110
443	P3 Research Ltd	Tauranga		New Zealand	3110
444	Clinical Horizons NZ Ltd	Tauranga		New Zealand	3112
445	P3 Research Ltd	Wellington		New Zealand	6021
446	Pacific Radiology	Wellington		New Zealand	6021
447	Unidad de Investigacion en Medicina Interna y Enfermedades criticas-Hogar Clinica San Juan de Dios	Cayma	Arequipa	Peru
448	Centro De Investigacion Clinica Trujillo EIRL/Clinica Peruano Americana S.A.	Trujillo	LA Libertad	Peru	13001
449	ABK REUMA S.R.L. de Medicentro Biociencias/BIO CIENCIAS PERU S.R.L.	Lima		Peru	21
450	Centro de Investigación Reumatología CAA-Clinica Anglo Americana	Lima		Peru	27
451	Investigaciones en Reumatologia / Centro Medico Corpac S.A.	Lima		Peru	27
452	Centro de Investigaciones Medicas-Hospital Maria Auxiliadora	Lima		Peru	29
453	Investigaciones Clinicas S.A.C. / Instituto de Ginecologia y Reproduccion S.A.	Lima		Peru	33
454	Investigaciones Clinicas S.A.C./Instituto de Ginecologia y Reproduccion S.A.	Lima		Peru	33
455	Philippine General Hospital	Manila	NCR	Philippines	1000
456	Manila Doctors Hospital	Manila		Philippines	1000
457	Moscow Municipal Rheumatology Center	Moscow		Russian Federation	119049
458	SBHI "City Clinical Hospital No. 1 n.a N.I. Pirogov"	Moscow		Russian Federation	119049
459	SBHI "City Clinical Hospital No. 1 n.a. N.I. Pirogov"	Moscow		Russian Federation	119049
460	Federal State Budgetary Scientific Research institution of fundamental and clinical immunology	Novosibirsk		Russian Federation	630047
461	Federal State Budgetary Scientific Institution	Novosibirsk		Russian Federation	630117
462	State Budgetary Institution of Ryazan Region	Ryazan		Russian Federation	390026
463	Medical Technologies Ltd	Saint Petersburg		Russian Federation	191025
464	Limited Liability Company "Medical Center "Reavita Med SPb"	Saint Petersburg		Russian Federation	194354
465	Medinet LLC	Saint Petersburg		Russian Federation	194356
466	FSBI 'SRITO n.a. R.R. Vreden' MoH RF	Saint Petersburg		Russian Federation	195427
467	Institute for Rehabilitation	Belgrade		Serbia	11000
468	Institute of Rheumatology	Belgrade		Serbia	11000
469	Institute for treatment and rehabilitation "Niska Banja"	Niska Banja		Serbia	18205
470	Special Hospital for Rheumatic Diseases Novi Sad	Novi Sad		Serbia	21000
471	General hospital "Dr Laza K. Lazarevic" Sabac	Sabac		Serbia	15000
472	Reumatologia s.r.o.	Bratislava		Slovakia	820 07
473	Nestatna Reumatologicka Ambulancia, Poliklinika Karlova Ves	Bratislava		Slovakia	841 04
474	MUDr. STRANAI s.r.o.	Kosice		Slovakia	040 11
475	Reum.hapi s.r.o.	Nove Mesto nad Vahom		Slovakia	91501
476	MEDIPA s.r.o.	Piestany		Slovakia	921 01
477	Thermium s.r.o.	Piestany		Slovakia	92101
478	Changhua Christian Hospital Clinical Trial Pharmacy	Changhua		Taiwan	500
479	Changhua Christian Hospital	Changhua		Taiwan	500
480	Chang Gung Memorial Hospital-Kaohsiung Branch Clinical Trial Pharmacy	Kaohsiung		Taiwan	83301
481	Chang Gung Memorial Hospital-Kaohsiung Branch	Kaohsiung		Taiwan	83301
482	Chung Shan Medical University Hospital Clinical Trial Pharmacy	Taichung		Taiwan	402
483	Chung Shan Medical University Hospital	Taichung		Taiwan	402
484	China Medical University Hospital	Taichung		Taiwan	40447
485	Department of Pharmacy, China Medical University Hospital	Taichung		Taiwan	40447
486	Regional Communal Institution Chernivtsi Regional Clinical Hospital	Chernivtsi		Ukraine	58001
487	Communal Non-profit Institution "City Clinical Hospital No.27" of Kharkiv City Council	Kharkiv		Ukraine	61002
488	Government Institution "L.T. Malaya Therapy National Institute of the NAMS of Ukraine"	Kharkiv		Ukraine	61039
489	Chair of Internal Medicine #2	Kyiv		Ukraine	01601
490	Oleksandrivska Clinical Hospital Of Kyiv	Kyiv		Ukraine	01601
491	Kyiv City Clinical Hospital 3,Rheumatology Department	Kyiv		Ukraine	02125
492	Clinic of NI "NSC"M.D.Strazhesko Institute of Cardiology" of NAMS of Ukraine,	Kyiv		Ukraine	03151
493	Polyclinic of Administration of Medical Services and Rehabilitation of State Stock Holding Company	Kyiv		Ukraine	04050
494	Clinic of SI "Institute of Gerontology named after D.F Chebotarov of NAMS of Ukraine"	Kyiv		Ukraine	04114
495	Clinic of SI Institute of Gerontology named after D.F Chebotarov of NAMS of Ukraine	Kyiv		Ukraine	04114
496	National Medical University named after O O Bogomolets,	Kyiv		Ukraine	04119
497	Polyclinic Of Administration of Medical Services and Rehabilitation of SSHC Artem	Kyiv		Ukraine	04119
498	Communal Non-profit Institution "City Clinical Hospital #5 of Lviv", Therapeutics Department	Lviv		Ukraine	79013
499	Communal Institution "Odesa Regional Clinical Hospital"	Odesa		Ukraine	65025
500	Multi-field Medical Center (University Clinic No.1) of Odesa National Medical University,	Odesa		Ukraine	65026
501	Communal Institution Ternopil University Hospital	Ternopil		Ukraine	46002
502	Vinnytsia Regional Clinical Hospital named after M.I. Pyrogov, Rheumatology Department,	Vinnytsia		Ukraine	21018
503	Communal Non-commercial Enterprise "Vinnytsia City Clinical Hospital No 1"	Vinnytsia		Ukraine	21029
504	Medical Clinical Investigational Centre of Medical Centre Health Clinic LTD	Vinnytsia		Ukraine	21029
505	Scientific and Research Institute of Invalid Rehabilitation (Educational and Scientific Medical	Vinnytsia		Ukraine	21029
506	Vinnytsya Medical National University named after M.I. Pyrogov, Chair of Internal Medicine #3	Vinnytsia		Ukraine	21029
507	Communal Institution Zaporizhzhya Regional Clinical Hospital	Zaporizhzhya		Ukraine	69600

Sponsors and Collaborators

• Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center, Pfizer

Study Documents (Full-Text)

• Statistical Analysis Plan - Mar 1, 2019
• Study Protocol - May 15, 2006

More Information

Additional Information:

• To obtain contact information for a study center near you, click here.

Publications

None provided.

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT02528188
• Other Study ID Numbers: A4091058; 2012-003721-22; OA SAFETY STUDY
• First Posted: Aug 19, 2015
• Last Update Posted: Jan 10, 2020
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Osteoarthritis; Osteoarthritis, Knee; Osteoarthritis, Hip; Chronic Pain; Tanezumab

Study Results

Participant Flow

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Period Title: Overall Study
STARTED	1008	1005	1008
Treated	1002	998	996
COMPLETED	741	729	757
NOT COMPLETED	267	276	251

Baseline Characteristics

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID	Total
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.	Total of all reporting groups
Overall Participants	1002	998	996	2996
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.30 (9.17)	61.15 (9.57)	60.25 (9.46)	60.57 (9.41)
Sex: Female, Male (Count of Participants)
Female	637 63.6%	654 65.5%	662 66.5%	1953 65.2%
Male	365 36.4%	344 34.5%	334 33.5%	1043 34.8%
Race/Ethnicity, Customized (Count of Participants)
White	705 70.4%	712 71.3%	680 68.3%	2097 70%
Black or African American	166 16.6%	162 16.2%	186 18.7%	514 17.2%
Asian	110 11%	95 9.5%	99 9.9%	304 10.1%
Other	21 2.1%	29 2.9%	31 3.1%	81 2.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Adjudicated Primary Composite Joint Safety Outcome
Description	Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive osteoarthritis (OA) type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of joint space width (JSW) (greater than or equal to [>=] 2 millimeters [mm]) within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [percentage of participants]	3.9 0.4%	7.1 0.7%	1.5 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0123
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	2.39
	Confidence Interval	(2-Sided) 95%; 0.58 to 4.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	5.61
	Confidence Interval	(2-Sided) 95%; 3.55 to 8.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Observation Time-Adjusted Event Rate of Participants With Adjudicated Primary Composite Joint Safety Outcome
Description	Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Primary joint safety outcome included participants with adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [events per 1000 participant-years]	38.3	71.5	14.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	23.5
	Confidence Interval	(2-Sided) 95%; 9.3 to 37.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	56.7
	Confidence Interval	(2-Sided) 95%; 38.4 to 74.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Week 16
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions, which may not be a whole (integer) number, scored on a numerical rating scale (NRS). Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Least Squares Mean (Standard Error) [units on a scale]	-3.22 (0.11)	-3.33 (0.11)	-3.07 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.0148
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -0.46 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. Analysis of covariance (ANCOVA) model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.1597
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

4. Primary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Week 16
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Least Squares Mean (Standard Error) [units on a scale]	-3.27 (0.11)	-3.39 (0.11)	-3.08 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.0030
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.52 to -0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.0691
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

5. Primary Outcome

Title	Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 16
Description	PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using Interactive Response Technology (IRT), where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Time Frame	Baseline, Week 16

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Least Squares Mean (Standard Error) [units on a scale]	-0.96 (0.04)	-0.97 (0.04)	-0.94 (0.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.3431
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments	A graphical testing procedure was applied to maintain Type I error. Tanezumab 5 mg versus NSAID was tested first and if all primary endpoints were found significant, then the testing was continued for Tanezumab 2.5 mg versus NSAID and the key secondary endpoint (>=50% reduction from baseline in WOMAC Pain at Week 16). Primary endpoints were tested sequentially within a dose in order of WOMAC pain, WOMAC physical function, and PGA.
Statistical Test of Hypothesis	p-Value	0.6332
	Comments	Threshold for significance at 0.05 level.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants With Adjudicated Secondary Composite Joint Safety Outcome
Description	Any participant with incidence of an adjudicated outcome of primary osteonecrosis, rapidly progressive OA type 2, subchondral insufficiency fracture, or pathological fracture. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [percentage of participants]	1.0 0.1%	2.2 0.2%	0.5 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4082
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -0.75 to 2.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0238
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; 0.31 to 3.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Observation Time-Adjusted Event Rate of Participants With Adjudicated Secondary Composite Joint Safety Outcome
Description	Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Secondary joint safety outcome included primary osteonecrosis, rapidly progressive OA (type-2), subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [events per 1000 participant-years]	9.7	21.8	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2035
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	4.8
	Confidence Interval	(2-Sided) 95%; -2.6 to 12.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	16.9
	Confidence Interval	(2-Sided) 95%; 6.8 to 27.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants With Individual Adjudicated Joint Safety Outcome
Description	Any participant with incidence of an adjudicated outcome of rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Rapidly progressive OA type 1 events were those that the Adjudication Committee considered to have significant loss of JSW >=2 mm within approximately 1 year without gross structural failure. Rapidly progressive OA type 2 events were those considered to have abnormal loss/destruction of bone including limited or total collapse of at least one subchondral surface (e.g., medial femoral condyle) that is not normally present in conventional end-stage OA.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Rapidly Progressive OA Type 1 or 2	3.2 0.3%	6.3 0.6%	1.2 0.1%
Rapidly Progressive OA type 1	2.9 0.3%	4.9 0.5%	1.1 0.1%
Rapidly Progressive OA type 2	0.3 0%	1.4 0.1%	0.1 0%
Primary Osteonecrosis	0.1 0%	0.1 0%	0 0%
Pathological Fracture	0 0%	0 0%	0 0%
Subchondral Insufficiency Fracture	0.6 0.1%	0.7 0.1%	0.4 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly progressive OA Type 1 or 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0248
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference
	Estimated Value	1.99
	Confidence Interval	(2-Sided) 95%; 0.31 to 4.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1 or 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	5.11
	Confidence Interval	(2-Sided) 95%; 3.16 to 7.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0366
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95%; 0.16 to 3.92
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	3.81
	Confidence Interval	(2-Sided) 95%; 1.99 to 6.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly Progressive OA Type 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6168
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.76 to 1.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0388
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.17 to 2.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Primary osteonecrosis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7245
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.74 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Primary osteonecrosis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7182
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 95%; -0.74 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Subchondral insufficiency fracture
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6824
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95%; -0.96 to 1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Subchondral insufficiency fracture
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5632
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk difference
	Estimated Value	0.30
	Confidence Interval	(2-Sided) 95%; -0.86 to 2.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Observation Time-Adjusted Event Rate of Participants With Individual Adjudicated Joint Safety Outcome
Description	Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Individual joint safety outcome included rapidly progressive OA (type-1 only), rapidly progressive OA (type-2 only), rapidly progressive OA (type-1 or type-2 combined), subchondral insufficiency fracture, primary osteonecrosis, and pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Rapidly Progressive OA Type 1 or 2	31.4	63.3	11.9
Rapidly Progressive OA Type 1	28.4	49.1	10.9
Rapidly Progressive OA Type 2	2.9	13.9	1.0
Primary Osteonecrosis	1.0	1.0	0
Pathological Fracture	0	0	0
Subchondral Insufficiency Fracture	5.8	6.9	3.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1 or 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0027
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	19.56
	Confidence Interval	(2-Sided) 95%; 6.78 to 32.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1 or 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	51.48
	Confidence Interval	(2-Sided) 95%; 34.47 to 68.50
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0047
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	17.58
	Confidence Interval	(2-Sided) 95%; 5.39 to 29.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 1
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	38.22
	Confidence Interval	(2-Sided) 95%; 23.05 to 53.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Rapidly Progressive OA Type 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3214
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; -1.89 to 5.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Rapidly Progressive OA Type 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	12.88
	Confidence Interval	(2-Sided) 95%; 5.36 to 20.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Subchondral Insufficiency Fracture
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5394
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; -4.17 to 7.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Subchondral Insufficiency Fracture
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3636
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	2.98
	Confidence Interval	(2-Sided) 95%; -3.44 to 9.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Primary osteonecrosis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Poisson model for rate difference
	Estimated Value	1.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was not estimable since there were less number of participants with events.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Primary osteonecrosis
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	1.0
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	95% CI was not estimable since there were less number of participants with events.

10. Secondary Outcome

Title	Percentage of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome
Description	Percentage of participants with total joint replacement (hip, knee or shoulder) or adjudicated primary composite joint safety outcomes were reported. Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [percentage of participants]	8.6 0.9%	13.1 1.3%	3.7 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	The event of adjudicated primary osteonecrosis in the tanezumab 2.5 mg treatment group is not included in this analysis. Conclusions for this analysis do not change as the comparison to NSAID is already statistically significant in favor of NSAID.
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	4.87
	Confidence Interval	(2-Sided) 95%; 2.43 to 7.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Exact methods for risk difference
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	9.41
	Confidence Interval	(2-Sided) 95%; 6.73 to 12.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Observation Time-Adjusted Event Rate of Participants With Total Joint Replacement or Adjudicated Primary Composite Joint Safety Outcome
Description	Observation time was defined as the start day of first SC study medication until either the (i) date of completion of or withdrawal from study, if a participant did not have the event, or (ii) date of the event (earliest event within each participant in the case of multiple events). Adjudicated primary composite joint safety outcomes included primary osteonecrosis, rapidly progressive OA type 1 or type 2, subchondral insufficiency fracture, or pathological fracture. Event rate was calculated as the number of events per 1000 participant-years at risk.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Number (95% Confidence Interval) [events per 1000 participant-years]	84.9	132.5	36.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	The event of adjudicated primary osteonecrosis in the tanezumab 2.5 mg treatment group is not included in this analysis. Conclusions for this analysis do not change as the comparison to NSAID is already statistically significant in favor of NSAID.
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	48.25
	Confidence Interval	(2-Sided) 95%; 26.76 to 69.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Poisson model for rate difference
	Comments
Method of Estimation	Estimation Parameter	Rate Difference
	Estimated Value	95.83
	Confidence Interval	(2-Sided) 95%; 70.25 to 121.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Medial or Lateral Joint Space Width of the Index Knee (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80
Description	Change from baseline in JSW was defined as change in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the medial and lateral tibiofemoral of knee in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral).
Time Frame	Baseline, Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	651	668	695
Change in Medial JSW at Week 56	-0.25 (0.03)	-0.34 (0.03)	-0.19 (0.03)
Change in Medial JSW at Week 80	-0.33 (0.04)	-0.37 (0.04)	-0.25 (0.03)
Change in Lateral JSW at Week 56	-0.26 (0.07)	-0.32 (0.07)	-0.27 (0.07)
Change in Lateral JSW at Week 80	-0.46 (0.08)	-0.32 (0.09)	-0.37 (0.08)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change in medial JSW width at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0979
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.15 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change in medial JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.24 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.04
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change in medial JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1162
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change in medial JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0128
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.22 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change in lateral JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8885
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change in lateral JSW at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6345
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change in lateral JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4406
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change in lateral JSW at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7109
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

13. Secondary Outcome

Title	Change From Baseline in Joint Space Width of the Index Hip (Kellgren-Lawrence Grade 2 or 3) at Weeks 56 and 80
Description	Change from baseline in JSW was defined as narrowing in JSW compared to baseline in participants with Kellgren-Lawrence grade 2 or 3 over the course of the study. It was measured radiographically in the index hip in participants with OA. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.
Time Frame	Baseline, Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	123	132	120
Change at Week 56	-0.35 (0.06)	-0.40 (0.06)	-0.21 (0.06)
Change at Week 80	-0.46 (0.07)	-0.35 (0.07)	-0.28 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1020
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 56: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0230
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.35 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0645
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 80: ANCOVA model included treatment, baseline JSW as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

14. Secondary Outcome

Title	Number of Participants With Progression of Osteoarthritis in the Index Knee (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80
Description	Progression of OA according to Bland-Altman as defined by a decrease JSW >=1.96 times within-participant standard deviation of change in JSW. The number of participants with progression of OA in the index knee are summarized separately by the compartment of OA at baseline (medial or lateral). Kellgren-Lawrence grade system was a method of classifying the severity of knee OA using five grades i.e. 0 [no radiographic features of OA], 1 [doubtful joint space narrowing (JSN) and possible osteophytic lipping], 2 [definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph], 3 [multiple osteophytes, definite JSN, sclerosis, possible bony deformity], 4 [large osteophytes, marked JSN, severe sclerosis and definite bony deformity]. Higher grade indicating worse knee function.
Time Frame	Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	651	668	695
Decreased medial JSW at Week 56	33 3.3%	43 4.3%	20 2%
Decreased medial JSW at Week 80	29 2.9%	38 3.8%	16 1.6%
Decreased lateral JSW at Week 56	5 0.5%	8 0.8%	9 0.9%
Decreased lateral JSW at Week 80	9 0.9%	4 0.4%	7 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease in medial JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0358
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.85
	Confidence Interval	(2-Sided) 95%; 1.04 to 3.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease in medial JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.37
	Confidence Interval	(2-Sided) 95%; 1.37 to 4.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease in medial JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0301
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.01
	Confidence Interval	(2-Sided) 95%; 1.07 to 3.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease in medial JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.65
	Confidence Interval	(2-Sided) 95%; 1.45 to 4.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease in lateral JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3002
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.18 to 1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease in lateral JSW at Week 56: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8997
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.39 to 2.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease in lateral JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4559
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; 0.53 to 4.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease in lateral JSW at Week 80: Logistic regression model included treatment, and baseline JSW as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5996
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.71
	Confidence Interval	(2-Sided) 95%; 0.20 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Number of Participants With Progression of Osteoarthritis in the Index Hip (Kellgren-Lawrence Grade 2 or 3) According to Bland and Altman Method at Weeks 56 and 80
Description	Progression of OA according to Bland-Altman methodology as defined by a decrease in JSW >=1.96 times within-participant standard deviation of the change in JSW in the index hip. The number of participants with progression of OA in the index hip per Bland-Altman methodology are reported. Kellgren-Lawrence grade system was a method of classifying the severity of hip OA using five grades i.e. 0 (no radiographic features of OA), 1 (doubtful JSN and possible osteophytic lipping), 2 (definite osteophytes and possible JSN on anteroposterior weight-bearing radiograph), 3 (multiple osteophytes, definite JSN, sclerosis, possible bony deformity), 4 (large osteophytes, marked JSN, severe sclerosis and definite bony deformity). Higher grade indicating worse hip function.
Time Frame	Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here "Overall number of participants analyzed" signifies participants who were evaluable for this outcome measure, and "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	123	132	120
Week 56	10 1%	10 1%	3 0.3%
Week 80	9 0.9%	9 0.9%	3 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease at Week 56: Logistic regression model included treatment, and baseline JSW as covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0714
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.37
	Confidence Interval	(2-Sided) 95%; 0.90 to 12.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease at Week 56: Logistic regression model included treatment, and baseline JSW as covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0681
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.42
	Confidence Interval	(2-Sided) 95%; 0.91 to 12.84
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Decrease at Week 80: Logistic regression model included treatment, and baseline JSW as covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0967
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.12
	Confidence Interval	(2-Sided) 95%; 0.81 to 11.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Decrease at Week 80: Logistic regression model included treatment, and baseline JSW as covariate
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0976
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	3.11
	Confidence Interval	(2-Sided) 95%; 0.81 to 11.90
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.65 (0.08)	-1.49 (0.08)	-1.55 (0.08)
Change at Week 4	-2.25 (0.09)	-2.29 (0.09)	-1.98 (0.09)
Change at Week 8	-2.41 (0.10)	-2.65 (0.10)	-2.27 (0.10)
Change at Week 24	-2.73 (0.13)	-2.86 (0.13)	-2.67 (0.13)
Change at Week 32	-2.64 (0.13)	-2.68 (0.13)	-2.57 (0.13)
Change at Week 40	-2.56 (0.13)	-2.57 (0.13)	-2.52 (0.13)
Change at Week 48	-2.54 (0.13)	-2.48 (0.13)	-2.47 (0.13)
Change at Week 56	-2.44 (0.13)	-2.37 (0.13)	-2.42 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2212
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4557
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 95%; -0.45 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1273
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6349
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1339
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.44 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6237
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4224
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7526
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7328
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5888
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9345
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8782
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7076
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

17. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Subscale at Week 64
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS, which may not be a whole (integer) number. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	7.01 (1.12)	7.02 (1.12)	6.96 (1.08)
Change at Week 64	-3.47 (2.45)	-3.12 (2.40)	-3.85 (2.07)

18. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Subscale at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame	Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.76 (0.08)	-1.64 (0.08)	-1.55 (0.08)
Change at Week 4	-2.29 (0.09)	-2.31 (0.09)	-1.96 (0.09)
Change at Week 8	-2.46 (0.10)	-2.69 (0.10)	-2.27 (0.10)
Change at Week 24	-2.78 (0.13)	-2.88 (0.13)	-2.66 (0.13)
Change at Week 32	-2.66 (0.13)	-2.67 (0.13)	-2.55 (0.13)
Change at Week 40	-2.56 (0.13)	-2.57 (0.13)	-2.50 (0.13)
Change at Week 48	-2.56 (0.14)	-2.49 (0.13)	-2.45 (0.13)
Change at Week 56	-2.45 (0.14)	-2.36 (0.13)	-2.41 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0150
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.37 to -0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3286
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0517
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 95%; -0.61 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3621
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0832
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4072
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3404
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6344
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5756
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4394
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7747
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7305
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint and highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC physical function subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7330
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.22 to 0.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

19. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Subscale at Week 64
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function refers to participant's ability to move around and perform usual activities of daily living. The WOMAC physical function subscale is a 17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours. It was calculated as mean of the scores from 17 individual questions, which may not be a whole (integer) number, scored on a NRS. Scores for each question and WOMAC physical function subscale score on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	7.09 (1.07)	7.08 (1.11)	6.99 (1.09)
Change at Week 64	-3.42 (2.40)	-3.12 (2.41)	-3.81 (2.12)

20. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 24, 32, 40, 48 and 56
Description	PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using IRT, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Time Frame	Baseline, Weeks 2, 4, 8, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-0.67 (0.03)	-0.67 (0.03)	-0.63 (0.03)
Change at Week 4	-0.81 (0.03)	-0.84 (0.03)	-0.69 (0.03)
Change at Week 8	-0.77 (0.03)	-0.85 (0.03)	-0.76 (0.03)
Change at Week 24	-0.74 (0.05)	-0.79 (0.05)	-0.74 (0.05)
Change at Week 32	-0.72 (0.05)	-0.71 (0.05)	-0.72 (0.05)
Change at Week 40	-0.70 (0.05)	-0.69 (0.05)	-0.69 (0.05)
Change at Week 48	-0.70 (0.05)	-0.66 (0.05)	-0.67 (0.05)
Change at Week 56	-0.65 (0.05)	-0.60 (0.05)	-0.66 (0.05)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2159
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2049
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.19 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.21 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7799
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.08 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0061
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.16 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.03
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9718
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3292
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.14 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9830
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9137
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8784
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9995
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6648
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7280
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8856
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Change at Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline PGA and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2814
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.05 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.05
	Estimation Comments

21. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment (PGA) of Osteoarthritis at Week 64
Description	PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip (index joint) affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, using IRT, where 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5= very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worsening of condition.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	3.49 (0.61)	3.46 (0.60)	3.44 (0.59)
Change at Week 64	-0.79 (0.96)	-0.64 (0.98)	-0.95 (0.96)

22. Secondary Outcome

Title	Percentage of Participants Meeting Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International (OMERACT-OARSI) Responder Index at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64
Description	Participants were considered as OMERACT-OARSI responders: if the change (improvement) from baseline to week of interest was >=50 percent and >= 2 units in either WOMAC pain subscale or physical function subscale score; if change (improvement) from baseline to week of interest was >=20 percent and >=1 unit in at least 2 of the following: 1) WOMAC pain subscale score, 2) WOMAC physical function subscale score, 3) PGA of OA. WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and PGA of OA (score: 1 [very good] to 5 [very poor], higher score = worse condition). Missing data was imputed using mixed baseline/last observation carried forward (BOCF/LOCF).
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). "Number analyzed"=participants who were evaluable for this outcome measure at specified time points.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Week 2	46.7 4.7%	43.7 4.4%	44.8 4.5%
Week 4	62.6 6.2%	62.7 6.3%	56.4 5.7%
Week 8	67.5 6.7%	70.3 7%	64.4 6.5%
Week 16	78.2 7.8%	78.3 7.8%	75.1 7.5%
Week 24	62.4 6.2%	64.8 6.5%	61.3 6.2%
Week 32	59.2 5.9%	59.9 6%	58.6 5.9%
Week 40	58.4 5.8%	58.7 5.9%	58.2 5.8%
Week 48	57.4 5.7%	56.2 5.6%	57.3 5.8%
Week 56	56.5 5.6%	54.5 5.5%	56.0 5.6%
Week 64	79.2 7.9%	75.2 7.5%	86.5 8.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4691
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5451
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0059
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0057
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.55
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1584
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0060
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	() 95%; 1.08 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1117
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1004
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6258
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1154
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8018
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5697
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9557
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8553
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9901
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5870
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8302
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4823
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

23. Secondary Outcome

Title	Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Reduction >=30 Percent (%), >=50%, >=70% and >=90% Response at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64
Description	Percentage of participants with reduction in WOMAC pain intensity of >= 30%, 50%, 70% and 90% at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64 compared to baseline were classified as responders to WOMAC pain subscale and are reported here. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint (knee or hip) during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Missing data was imputed using mixed BOCF/LOCF.
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). "Number analyzed"=participants who were evaluable for this outcome measure at specified time points.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Week 2: At least 30% reduction	34.8 3.5%	30.5 3.1%	32.4 3.3%
Week 2: At least 50% reduction	17.8 1.8%	16.5 1.7%	14.7 1.5%
Week 2: At least 70% reduction	7.7 0.8%	7.1 0.7%	6.2 0.6%
Week 2: At least 90% reduction	2.4 0.2%	2.5 0.3%	1.8 0.2%
Week 4: At least 30% reduction	50.2 5%	49.5 5%	44.4 4.5%
Week 4: At least 50% reduction	30.4 3%	30.5 3.1%	24.9 2.5%
Week 4: At least 70% reduction	14.5 1.4%	16.4 1.6%	11.9 1.2%
Week 4: At least 90% reduction	4.3 0.4%	4.9 0.5%	3.1 0.3%
Week 8: At least 30% reduction	55.9 5.6%	59.0 5.9%	54.1 5.4%
Week 8: At least 50% reduction	36.8 3.7%	39.3 3.9%	32.6 3.3%
Week 8: At least 70% reduction	19.3 1.9%	22.4 2.2%	15.9 1.6%
Week 8: At least 90% reduction	4.7 0.5%	6.6 0.7%	4.2 0.4%
Week 16: At least 30% reduction	71.8 7.2%	72.9 7.3%	68.9 6.9%
Week 16: At least 50% reduction	54.9 5.5%	56.5 5.7%	51.5 5.2%
Week 16: At least 70% reduction	28.9 2.9%	35.0 3.5%	28.8 2.9%
Week 16: At least 90% reduction	10.3 1%	12.7 1.3%	8.5 0.9%
Week 24: At least 30% reduction	59.4 5.9%	61.1 6.1%	59.4 6%
Week 24: At least 50% reduction	49.3 4.9%	49.4 4.9%	47.5 4.8%
Week 24: At least 70% reduction	30.8 3.1%	33.8 3.4%	29.0 2.9%
Week 24: At least 90% reduction	10.3 1%	13.3 1.3%	11.5 1.2%
Week 32: At least 30% reduction	56.8 5.7%	55.7 5.6%	56.3 5.7%
Week 32: At least 50% reduction	47.4 4.7%	45.8 4.6%	46.3 4.6%
Week 32: At least 70% reduction	31.2 3.1%	31.5 3.2%	27.4 2.8%
Week 32: At least 90% reduction	10.3 1%	12.9 1.3%	10.0 1%
Week 40: At least 30% reduction	55.7 5.6%	54.6 5.5%	54.8 5.5%
Week 40: At least 50% reduction	47.2 4.7%	45.2 4.5%	46.0 4.6%
Week 40: At least 70% reduction	30.0 3%	30.4 3%	29.3 2.9%
Week 40: At least 90% reduction	10.8 1.1%	12.0 1.2%	10.4 1%
Week 48: At least 30% reduction	54.6 5.4%	52.9 5.3%	54.2 5.4%
Week 48: At least 50% reduction	46.2 4.6%	43.2 4.3%	44.4 4.5%
Week 48: At least 70% reduction	29.6 3%	29.4 2.9%	28.5 2.9%
Week 48: At least 90% reduction	10.3 1%	11.4 1.1%	10.6 1.1%
Week 56: At least 30% reduction	53.1 5.3%	51.2 5.1%	52.7 5.3%
Week 56: At least 50% reduction	44.3 4.4%	41.5 4.2%	43.5 4.4%
Week 56: At least 70% reduction	28.2 2.8%	27.0 2.7%	27.5 2.8%
Week 56: At least 90% reduction	10.1 1%	10.5 1.1%	10.1 1%
Week 64: At least 30% reduction	73.0 7.3%	69.0 6.9%	81.3 8.2%
Week 64: At least 50% reduction	55.4 5.5%	47.3 4.7%	60.2 6%
Week 64: At least 70% reduction	31.1 3.1%	24.3 2.4%	34.2 3.4%
Week 64: At least 90% reduction	9.6 1%	7.9 0.8%	12.6 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2938
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3146
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0748
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3000
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2550
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4780
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4006
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.30
	Confidence Interval	(2-Sided) 95%; 0.70 to 2.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3089
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 0.74 to 2.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0114
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0239
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.23
	Confidence Interval	(2-Sided) 95%; 1.03 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0079
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0068
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1037
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0046
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.12 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1971
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 0.85 to 2.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0480
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.59
	Confidence Interval	(2-Sided) 95%; 1.00 to 2.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4744
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0336
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0559
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.20
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 1.11 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0535
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95%; 1.22 to 1.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6421
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0207
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.60
	Confidence Interval	(2-Sided) 95%; 1.07 to 2.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1635
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.95 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0529
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=50% reduction
	Type of Statistical Test	Superiority
	Comments	The two key secondary comparisons for 'Participants with >=50% reduction from baseline in WOMAC Pain at Week 16' (tanezumab 2.5 mg treatment group versus NSAID and tanezumab 5 mg treatment group versus NSAID) could not be considered significant since preceding tests in the graphical testing procedure were not significant.
Statistical Test of Hypothesis	p-Value	0.1322
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=50% reduction
	Type of Statistical Test	Superiority
	Comments	The two key secondary comparisons for 'Participants with >=50% reduction from baseline in WOMAC Pain at Week 16' (tanezumab 2.5 mg treatment group versus NSAID and tanezumab 5 mg treatment group versus NSAID) could not be considered significant since preceding tests in the graphical testing procedure were not significant.
Statistical Test of Hypothesis	p-Value	0.0262
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9805
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0033
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 1.10 to 1.61
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1590
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.69
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0024
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.57
	Confidence Interval	(2-Sided) 95%; 1.17 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9932
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4374
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4406
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4078
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4071
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0248
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.24
	Confidence Interval	(2-Sided) 95%; 1.03 to 1.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3641
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2497
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.53
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8682
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7317
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6493
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7973
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0757
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0578
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 0.99 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9010
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0548
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.32
	Confidence Interval	(2-Sided) 95%; 0.99 to 1.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7331
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8632
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.98
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6262
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6817
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7990
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6786
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8069
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2951
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.54
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9093
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5032
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4382
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5638
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 61

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6436
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 62

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7060
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 63

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7729
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 64

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6405
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 65

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9046
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 66

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4491
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 67

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7429
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 68

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3467
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 69

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7624
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 70

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7686
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 71

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9384
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

Statistical Analysis 72

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8495
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.

24. Secondary Outcome

Title	Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale at Weeks 16, 24 and 56
Description	WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. The WOMAC pain subscale is a 5-item questionnaire used to assess the amount of pain experienced due to OA of index joint during past 48 hours. It was calculated as the mean of scores from 5 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale score on NRS ranged from 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain. Percentage of participants with cumulative reduction (as percent) (greater than [>] 0% ; >= 10, 20, 30, 40, 50, 60, 70, 80 and 90%; = 100 %) in WOMAC pain subscale from Baseline to Weeks 16, 24 and 56 were reported, participants (%) are reported more than once in categories specified. Missing data was imputed using mixed BOCF/LOCF.
Time Frame	Baseline, Weeks 16, 24 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Week 16: >0%	89.5 8.9%	87.6 8.8%	87.1 8.7%
Week 16: >=10%	85.0 8.5%	82.8 8.3%	82.8 8.3%
Week 16: >=20%	78.1 7.8%	78.3 7.8%	75.8 7.6%
Week 16: >=30%	71.8 7.2%	72.9 7.3%	68.9 6.9%
Week 16: >=40%	63.7 6.4%	63.5 6.4%	59.9 6%
Week 16: >=50%	54.9 5.5%	56.5 5.7%	51.5 5.2%
Week 16: >=60%	40.9 4.1%	44.8 4.5%	38.8 3.9%
Week 16: >=70%	28.9 2.9%	35.0 3.5%	28.8 2.9%
Week 16: >=80%	19.4 1.9%	23.9 2.4%	18.8 1.9%
Week 16: >=90%	10.3 1%	12.7 1.3%	8.5 0.9%
Week 16: =100%	4.4 0.4%	3.9 0.4%	3.3 0.3%
Week 24: >0%	66.7 6.7%	68.2 6.8%	64.8 6.5%
Week 24: >=10%	64.9 6.5%	66.4 6.7%	63.4 6.4%
Week 24: >=20%	62.2 6.2%	65.2 6.5%	62.1 6.2%
Week 24: >=30%	59.4 5.9%	61.1 6.1%	59.4 6%
Week 24: >=40%	55.2 5.5%	55.7 5.6%	54.7 5.5%
Week 24: >=50%	49.3 4.9%	49.4 4.9%	47.5 4.8%
Week 24: >=60%	40.7 4.1%	41.2 4.1%	38.1 3.8%
Week 24: >=70%	30.8 3.1%	33.8 3.4%	29.0 2.9%
Week 24: >=80%	20.6 2.1%	24.0 2.4%	20.2 2%
Week 24: >=90%	10.3 1%	13.3 1.3%	11.5 1.2%
Week 24: =100%	3.9 0.4%	4.5 0.5%	3.4 0.3%
Week 56: >0%	60.8 6.1%	59.1 5.9%	59.7 6%
Week 56: >=10%	59.1 5.9%	57.0 5.7%	58.1 5.8%
Week 56: >=20%	55.9 5.6%	54.8 5.5%	56.3 5.7%
Week 56: >=30%	53.1 5.3%	51.2 5.1%	52.7 5.3%
Week 56: >=40%	48.6 4.9%	46.8 4.7%	48.6 4.9%
Week 56: >=50%	44.3 4.4%	41.5 4.2%	43.5 4.4%
Week 56: >=60%	37.0 3.7%	33.8 3.4%	36.3 3.6%
Week 56: >=70%	28.2 2.8%	27.0 2.7%	27.5 2.8%
Week 56: >=80%	18.9 1.9%	19.1 1.9%	18.6 1.9%
Week 56: >=90%	10.1 1%	10.5 1.1%	10.1 1%
Week 56: =100%	4.5 0.4%	5.3 0.5%	4.1 0.4%

25. Secondary Outcome

Title	Percentage of Participants Achieving Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale Reduction of >=30%, >=50%, >=70% and >=90% Response at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64
Description	Percentage of participants with reduction in WOMAC physical function of >=(30%,50%,70%,90%) at Weeks 2,4,8,16,24,32,40,48,56 and 64 compared to baseline were classified as responders to WOMAC physical function subscale. WOMAC: Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function:Participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale17-item questionnaire used to assess the degree of difficulty experienced due to OA in index joint (knee/hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC physical subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), where higher scores indicated extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). "Overall number of participants analyzed" = participants who were evaluable for this outcome measure. "Number analyzed"=participants who were evaluable for this outcome measure at specified time points.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Week 2: At least 30% reduction	35.8 3.6%	32.1 3.2%	31.7 3.2%
Week 2: At least 50% reduction	20.0 2%	17.0 1.7%	15.4 1.5%
Week 2: At least 70% reduction	8.3 0.8%	8.2 0.8%	5.8 0.6%
Week 2: At least 90% reduction	2.1 0.2%	3.2 0.3%	1.7 0.2%
Week 4: At least 30% reduction	49.0 4.9%	49.1 4.9%	43.2 4.3%
Week 4: At least 50% reduction	31.1 3.1%	31.3 3.1%	23.1 2.3%
Week 4: At least 70% reduction	15.5 1.5%	15.8 1.6%	11.2 1.1%
Week 4: At least 90% reduction	4.6 0.5%	5.4 0.5%	2.6 0.3%
Week 8: At least 30% reduction	56.0 5.6%	59.5 6%	55.0 5.5%
Week 8: At least 50% reduction	36.6 3.7%	40.0 4%	31.4 3.2%
Week 8: At least 70% reduction	18.7 1.9%	21.3 2.1%	14.1 1.4%
Week 8: At least 90% reduction	5.8 0.6%	7.1 0.7%	4.4 0.4%
Week 16: At least 30% reduction	71.6 7.1%	71.8 7.2%	68.1 6.8%
Week 16: At least 50% reduction	53.1 5.3%	55.8 5.6%	50.1 5%
Week 16: At least 70% reduction	29.9 3%	34.3 3.4%	27.9 2.8%
Week 16: At least 90% reduction	10.7 1.1%	13.4 1.3%	9.7 1%
Week 24: At least 30% reduction	59.5 5.9%	61.3 6.1%	59.0 5.9%
Week 24: At least 50% reduction	49.9 5%	48.2 4.8%	46.8 4.7%
Week 24: At least 70% reduction	30.4 3%	32.7 3.3%	27.8 2.8%
Week 24: At least 90% reduction	11.0 1.1%	13.0 1.3%	9.8 1%
Week 32: At least 30% reduction	56.7 5.7%	56.6 5.7%	55.9 5.6%
Week 32: At least 50% reduction	47.2 4.7%	45.7 4.6%	44.7 4.5%
Week 32: At least 70% reduction	29.7 3%	30.2 3%	26.8 2.7%
Week 32: At least 90% reduction	11.0 1.1%	13.1 1.3%	9.4 0.9%
Week 40: At least 30% reduction	55.5 5.5%	55.5 5.6%	54.9 5.5%
Week 40: At least 50% reduction	45.5 4.5%	45.0 4.5%	45.0 4.5%
Week 40: At least 70% reduction	29.5 2.9%	29.1 2.9%	27.6 2.8%
Week 40: At least 90% reduction	10.3 1%	13.2 1.3%	9.5 1%
Week 48: At least 30% reduction	54.5 5.4%	53.3 5.3%	54.6 5.5%
Week 48: At least 50% reduction	45.3 4.5%	43.5 4.4%	43.4 4.4%
Week 48: At least 70% reduction	29.1 2.9%	27.9 2.8%	26.1 2.6%
Week 48: At least 90% reduction	10.2 1%	12.0 1.2%	9.4 0.9%
Week 56: At least 30% reduction	52.0 5.2%	51.1 5.1%	52.9 5.3%
Week 56: At least 50% reduction	44.1 4.4%	41.3 4.1%	42.5 4.3%
Week 56: At least 70% reduction	26.9 2.7%	26.4 2.6%	26.0 2.6%
Week 56: At least 90% reduction	9.3 0.9%	10.5 1.1%	9.0 0.9%
Week 64: At least 30% reduction	71.4 7.1%	68.0 6.8%	78.2 7.9%
Week 64: At least 50% reduction	52.9 5.3%	44.6 4.5%	58.9 5.9%
Week 64: At least 70% reduction	31.4 3.1%	22.9 2.3%	33.9 3.4%
Week 64: At least 90% reduction	9.4 0.9%	7.9 0.8%	13.3 1.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0651
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.99 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9032
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0100
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.36
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3728
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0434
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.01 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0425
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.01 to 2.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5442
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.64 to 2.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0349
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.90
	Confidence Interval	(2-Sided) 95%; 1.05 to 3.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0108
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.26
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0080
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.27
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.50
	Confidence Interval	(2-Sided) 95%; 1.22 to 1.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.51
	Confidence Interval	(2-Sided) 95%; 1.24 to 1.85
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0060
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.11 to 1.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.49
	Confidence Interval	(2-Sided) 95%; 1.14 to 1.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.76
	Confidence Interval	(2-Sided) 95%; 1.08 to 2.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.12
	Confidence Interval	(2-Sided) 95%; 1.31 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7613
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0548
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0196
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 1.04 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.45
	Confidence Interval	(2-Sided) 95%; 1.20 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0077
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.39
	Confidence Interval	() 95%; 1.09 to 1.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.65
	Confidence Interval	(2-Sided) 95%; 1.30 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1942
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.31
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0122
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.64
	Confidence Interval	(2-Sided) 95%; 1.11 to 2.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0977
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0806
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95%; 0.98 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2097
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0135
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3571
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 1.11 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4658
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0108
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8393
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2977
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1944
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5714
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2472
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0235
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 1.03 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4074
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.13
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0296
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 1.03 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7607
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7979
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2964
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.92 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6950
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1985
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.93 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1239
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.96 to 1.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2762
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.18
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0121
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.44
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8443
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8472
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8980
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9385
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4261
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5250
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6273
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0132
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.43
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.90
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9095
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5098
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4488
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9757
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 61

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1843
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.14
	Confidence Interval	(2-Sided) 95%; 0.94 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 62

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4356
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 63

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6342
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 64

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0810
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.29
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 65

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6527
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 66

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=30% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3857
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 67

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5280
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio, log
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 68

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=50% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5355
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 69

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7732
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 70

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=70% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9397
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 71

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9044
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

Statistical Analysis 72

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: >=90% reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3193
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.16
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.57
	Parameter Dispersion	Type: Value:
	Estimation Comments	OR and 95% CI estimated from logistic regression model.Logistic regression model included baseline WOMAC physical function subscale,baseline diary average pain,classification variables index joint,highest Kellgren-Lawrence grade,NSAID and treatment.

26. Secondary Outcome

Title	Percentage of Participants With Cumulative Percent Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function Subscale at Weeks 16, 24 and 56
Description	Percentage of participants with cumulative reduction (as percent) (> 0 %; >= 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80% and 90%; =100%) in WOMAC physical function subscale from baseline to Weeks 16, 24 and 56 were reported. WOMAC:Self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Physical function: participant's ability to move around and perform usual activities of daily living. WOMAC physical function subscale:17-item questionnaire to assess the degree of difficulty experienced due to OA in index joint (knee or hip) during past 48 hours, calculated as mean of the scores from 17 individual questions scored on a NRS. Scores for each question and WOMAC Pain subscale on NRS ranged from 0 (no difficulty) to 10 (extreme difficulty), higher scores indicate extreme difficulty/worse physical function. Missing data was imputed using mixed BOCF/LOCF.
Time Frame	Baseline, Weeks 16, 24 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Week 16: >0%	90.0 9%	88.8 8.9%	87.4 8.8%
Week 16: >=10%	85.0 8.5%	83.9 8.4%	81.4 8.2%
Week 16: >=20%	78.4 7.8%	77.3 7.7%	73.7 7.4%
Week 16: >=30%	71.6 7.1%	71.8 7.2%	68.1 6.8%
Week 16: >=40%	63.7 6.4%	64.1 6.4%	61.0 6.1%
Week 16: >=50%	53.1 5.3%	55.8 5.6%	50.1 5%
Week 16: >=60%	41.4 4.1%	44.7 4.5%	39.8 4%
Week 16: >=70%	29.9 3%	34.3 3.4%	27.9 2.8%
Week 16: >=80%	20.8 2.1%	24.4 2.4%	17.9 1.8%
Week 16: >=90%	10.7 1.1%	13.4 1.3%	9.7 1%
Week 16: =100%	2.9 0.3%	3.3 0.3%	2.0 0.2%
Week 24: >0%	66.7 6.7%	68.6 6.9%	65.0 6.5%
Week 24: >=10%	65.0 6.5%	66.6 6.7%	63.3 6.4%
Week 24: >=20%	62.6 6.2%	64.2 6.4%	60.8 6.1%
Week 24: >=30%	59.5 5.9%	61.3 6.1%	59.0 5.9%
Week 24: >=40%	54.9 5.5%	56.0 5.6%	53.9 5.4%
Week 24: >=50%	49.9 5%	48.2 4.8%	46.8 4.7%
Week 24: >=60%	41.3 4.1%	42.0 4.2%	37.7 3.8%
Week 24: >=70%	30.4 3%	32.7 3.3%	27.8 2.8%
Week 24: >=80%	19.9 2%	22.6 2.3%	18.9 1.9%
Week 24: >=90%	11.0 1.1%	13.0 1.3%	9.8 1%
Week 24: =100%	3.0 0.3%	3.2 0.3%	2.7 0.3%
Week 56: >0%	61.1 6.1%	59.5 6%	60.1 6%
Week 56: >=10%	59.3 5.9%	57.3 5.7%	57.8 5.8%
Week 56: >=20%	56.1 5.6%	54.3 5.4%	55.4 5.6%
Week 56: >=30%	52.0 5.2%	51.1 5.1%	52.9 5.3%
Week 56: >=40%	48.5 4.8%	46.3 4.6%	48.9 4.9%
Week 56: >=50%	44.1 4.4%	41.3 4.1%	42.5 4.3%
Week 56: >=60%	36.7 3.7%	34.6 3.5%	34.8 3.5%
Week 56: >=70%	26.9 2.7%	26.4 2.6%	26.0 2.6%
Week 56: >=80%	17.1 1.7%	17.1 1.7%	17.4 1.7%
Week 56: >=90%	9.3 0.9%	10.5 1.1%	9.0 0.9%
Week 56: =100%	2.9 0.3%	3.6 0.4%	3.3 0.3%

27. Secondary Outcome

Title	Percentage of Participants Achieving Improvement of >=2 Points in Patient's Global Assessment (PGA) of Osteoarthritis at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64
Description	PGA of OA was assessed by asking a question from participants: "Considering all the ways your OA in your knee or hip affects you, how are you doing today?" Participants responded on a scale ranging from 1-5, where, 1=very good (no symptom and no limitation of normal activities), 2= good (mild symptoms and no limitation of normal activities), 3= fair (moderate symptoms and limitation of some normal activities), 4= poor (severe symptoms and inability to carry out most normal activities), and 5 = very poor (very severe symptoms and inability to carry out all normal activities). Higher scores indicated worse condition. Percentage of participants with improvement of at least 2 points from baseline in PGA of OA were reported. Missing data was imputed using mixed BOCF/LOCF.
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). "Overall number of participants analyzed" = participants who were evaluable for this outcome measure. "Number analyzed"=participants who were evaluable for this outcome measure at specified time points.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Week 2	14.6 1.5%	15.6 1.6%	11.6 1.2%
Week 4	21.4 2.1%	22.4 2.2%	15.9 1.6%
Week 8	21.9 2.2%	23.7 2.4%	19.0 1.9%
Week 16	29.1 2.9%	30.3 3%	28.2 2.8%
Week 24	23.4 2.3%	24.8 2.5%	23.7 2.4%
Week 32	23.7 2.4%	22.3 2.2%	23.6 2.4%
Week 40	21.7 2.2%	21.7 2.2%	21.0 2.1%
Week 48	22.0 2.2%	21.7 2.2%	21.1 2.1%
Week 56	21.0 2.1%	19.7 2%	20.8 2.1%
Week 64	21.1 2.1%	17.4 1.7%	25.8 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1772
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.91 to 1.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0154
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.42
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0105
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 95%; 1.08 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.63
	Confidence Interval	(2-Sided) 95%; 1.26 to 2.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4007
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.43
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0116
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.37
	Confidence Interval	(2-Sided) 95%; 1.07 to 1.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6279
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4674
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.09
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3135
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.71 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7581
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4504
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2629
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6763
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9456
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.27
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7520
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.76 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9981
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5284
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline PGA of OA scale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3220
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Change From Baseline in Average Pain Score in the Index Joint at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, 48 and 56
Description	Participants assessed their average pain in the index hip/knee in the past 24 hours using NRS, with a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data for Weeks 20 through 56 represents averages of the values reported during the 4-week interval up to and including the given week. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.
Time Frame	Baseline, Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 1	-0.47 (0.05)	-0.56 (0.05)	-0.56 (0.05)
Change at Week 2	-1.02 (0.07)	-0.97 (0.07)	-0.91 (0.07)
Change at Week 3	-1.40 (0.08)	-1.30 (0.08)	-1.23 (0.08)
Change at Week 4	-1.62 (0.09)	-1.65 (0.09)	-1.32 (0.09)
Change at Week 6	-1.85 (0.09)	-1.97 (0.09)	-1.49 (0.09)
Change at Week 8	-1.83 (0.10)	-2.04 (0.10)	-1.59 (0.10)
Change at Week 10	-2.35 (0.10)	-2.46 (0.10)	-1.98 (0.10)
Change at Week 12	-2.48 (0.10)	-2.55 (0.10)	-2.10 (0.10)
Change at Week 16	-2.41 (0.10)	-2.52 (0.10)	-2.17 (0.11)
Change at Week 20	-2.56 (0.11)	-2.60 (0.11)	-2.27 (0.11)
Change at Week 24	-2.35 (0.13)	-2.41 (0.12)	-2.11 (0.12)
Change at Week 32	-2.27 (0.13)	-2.26 (0.13)	-2.06 (0.13)
Change at Week 40	-2.25 (0.13)	-2.20 (0.13)	-2.07 (0.13)
Change at Week 48	-2.20 (0.13)	-2.10 (0.13)	-2.03 (0.13)
Change at Week 56	-2.17 (0.13)	-2.03 (0.13)	-2.04 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 1: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1120
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.09
	Confidence Interval	(2-Sided) 95%; -0.02 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 1: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9686
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.11 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.06
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1589
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4720
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.20 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 3: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0320
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.33 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 3: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3336
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.47 to -0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 6: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 6: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.66 to -0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0115
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.42 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.63 to -0.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 10: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.36
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 10: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.67 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.37
	Confidence Interval	(2-Sided) 95%; -0.57 to -0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 12: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 95%; -0.64 to -0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0238
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.44 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.55 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 20: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0064
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.30
	Confidence Interval	(2-Sided) 95%; -0.51 to -0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 20: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0589
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.48 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0180
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0944
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1198
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.45 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1837
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3170
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1873
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5719
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3571
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline pain in the index joint as covariate, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9072
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

29. Secondary Outcome

Title	Change From Baseline in Average Pain Score in the Index Joint at Week 64
Description	Participants assessed their average pain in the index hip/knee in the past 24 hours using NRS, with a scale ranging from 0 (no pain) to 10 (worst possible pain). Higher scores indicated higher pain. Data represents averages of the values reported during the 4-week interval up to and including Week 64. Change from baseline was calculated using the difference between each post-baseline weekly mean and the baseline mean score.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	6.76 (1.59)	6.77 (1.58)	6.76 (1.54)
Change at Week 64	-3.01 (2.60)	-2.81 (2.71)	-3.24 (2.55)

30. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.79 (0.09)	-1.70 (0.09)	-1.48 (0.09)
Change at Week 4	-2.32 (0.10)	-2.43 (0.10)	-1.95 (0.10)
Change at Week 8	-2.46 (0.10)	-2.79 (0.10)	-2.16 (0.10)
Change at Week 16	-3.32 (0.11)	-3.54 (0.11)	-3.10 (0.11)
Change at Week 24	-2.77 (0.13)	-2.95 (0.13)	-2.63 (0.13)
Change at Week 32	-2.68 (0.13)	-2.74 (0.13)	-2.52 (0.13)
Change at Week 40	-2.58 (0.14)	-2.64 (0.14)	-2.46 (0.14)
Change at Week 48	-2.60 (0.14)	-2.54 (0.13)	-2.44 (0.14)
Change at Week 56	-2.46 (0.14)	-2.46 (0.14)	-2.42 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.49 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0134
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.40 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.38
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.67 to -0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0031
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 95%; -0.49 to -0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.63
	Confidence Interval	(2-Sided) 95%; -0.82 to -0.43
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0425
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.43 to -0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.44
	Confidence Interval	(2-Sided) 95%; -0.65 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2980
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0179
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.32
	Confidence Interval	(2-Sided) 95%; -0.58 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2328
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1019
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.22
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2149
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.45 to 0.10
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2442
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.43 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4609
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8129
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC stiffness subscale and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7883
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

31. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Subscale at Week 64
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA. Stiffness was defined as a sensation of decreased ease of movement in the index joint (knee or hip). The WOMAC stiffness subscale is a 2-item questionnaire used to assess the amount of stiffness experienced due to OA in the index joint (knee or hip) during the past 48 hours. It was calculated as the mean of scores from 2 individual questions scored on NRS. Scores for each question and WOMAC stiffness subscale score on NRS ranged from 0 (no stiffness) to 10 (extreme stiffness), where higher scores indicated higher stiffness.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	7.15 (1.42)	7.20 (1.40)	7.09 (1.42)
Change at Week 64	-3.31 (2.72)	-3.04 (2.64)	-3.66 (2.36)

32. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.73 (0.08)	-1.61 (0.08)	-1.52 (0.08)
Change at Week 4	-2.28 (0.09)	-2.34 (0.09)	-1.95 (0.09)
Change at Week 8	-2.44 (0.10)	-2.71 (0.10)	-2.23 (0.10)
Change at Week 16	-3.26 (0.11)	-3.41 (0.11)	-3.07 (0.11)
Change at Week 24	-2.74 (0.13)	-2.88 (0.13)	-2.64 (0.13)
Change at Week 32	-2.65 (0.13)	-2.69 (0.13)	-2.54 (0.13)
Change at Week 40	-2.57 (0.13)	-2.58 (0.13)	-2.49 (0.13)
Change at Week 48	-2.56 (0.13)	-2.48 (0.13)	-2.44 (0.13)
Change at Week 56	-2.45 (0.13)	-2.38 (0.13)	-2.40 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0119
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.37 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3073
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 95%; -0.50 to -0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.39
	Confidence Interval	(2-Sided) 95%; -0.56 to -0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0251
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 95%; -0.39 to -0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -0.66 to -0.30
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0625
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -0.39 to 0.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0010
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.36 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0530
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.50 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4074
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.37 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2629
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5582
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.34 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4907
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.35 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4043
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7663
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7415
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.31 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC average score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8688
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.24 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

33. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Average Score at Week 64
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA of index joint (knee or hip). WOMAC pain subscale assess amount of pain experienced (score: 0 [no pain] to 10 [extreme pain], higher score = more pain), WOMAC physical function subscale assess degree of difficulty experienced (score: 0 [no difficulty] to 10 [extreme difficulty], higher score = worse physical function) and WOMAC stiffness subscale assess the amount of stiffness experienced (score: 0 [no stiffness] to 10 [extreme stiffness], higher score = higher stiffness). WOMAC average score was the mean of WOMAC pain, physical function and stiffness subscale scores and ranges from 0 to 10, where higher scores indicated worse response.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	7.09 (1.08)	7.10 (1.10)	7.01 (1.08)
Change at Week 64	-3.40 (2.40)	-3.09 (2.37)	-3.77 (2.06)

34. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.54 (0.08)	-1.39 (0.08)	-1.46 (0.08)
Change at Week 4	-2.14 (0.10)	-2.15 (0.10)	-1.91 (0.10)
Change at Week 8	-2.26 (0.10)	-2.47 (0.10)	-2.22 (0.10)
Change at Week 16	-3.01 (0.11)	-3.13 (0.11)	-2.95 (0.11)
Change at Week 24	-2.64 (0.13)	-2.76 (0.13)	-2.60 (0.13)
Change at Week 32	-2.54 (0.13)	-2.54 (0.13)	-2.52 (0.14)
Change at Week 40	-2.48 (0.14)	-2.42 (0.14)	-2.48 (0.14)
Change at Week 48	-2.45 (0.14)	-2.34 (0.14)	-2.42 (0.14)
Change at Week 56	-2.37 (0.14)	-2.21 (0.14)	-2.39 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3622
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3894
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.07
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0137
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.42 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0106
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.24
	Confidence Interval	(2-Sided) 95%; -0.43 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7179
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.23 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0120
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.44 to -0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5372
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0899
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.18
	Confidence Interval	(2-Sided) 95%; -0.40 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7646
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2547
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.41 to 0.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8806
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.29 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8416
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9981
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6485
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8317
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5819
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.19 to 0.35
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8538
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.26 to 0.31
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when walking on a flat surface and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1981
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; -0.10 to 0.47
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

35. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Walking on a Flat Surface at Week 64
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when walking on a flat surface?". Participants responded about the amount of pain they experienced when walking on a flat surface by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	6.86 (1.33)	6.90 (1.34)	6.86 (1.30)
Change at Week 64	-3.20 (2.78)	-2.69 (2.58)	-3.67 (2.32)

36. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 2	-1.81 (0.08)	-1.66 (0.08)	-1.66 (0.09)
Change at Week 4	-2.34 (0.10)	-2.43 (0.10)	-2.08 (0.10)
Change at Week 8	-2.48 (0.10)	-2.81 (0.10)	-2.40 (0.10)
Change at Week 16	-3.34 (0.11)	-3.50 (0.11)	-3.18 (0.12)
Change at Week 24	-2.89 (0.13)	-3.03 (0.13)	-2.83 (0.14)
Change at Week 32	-2.76 (0.14)	-2.84 (0.14)	-2.74 (0.14)
Change at Week 40	-2.69 (0.14)	-2.74 (0.14)	-2.70 (0.14)
Change at Week 48	-2.70 (0.14)	-2.63 (0.14)	-2.67 (0.14)
Change at Week 56	-2.55 (0.14)	-2.47 (0.14)	-2.55 (0.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0846
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9749
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.00
	Confidence Interval	(2-Sided) 95%; -0.18 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -0.45 to -0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 95%; -0.54 to -0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4402
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.41
	Confidence Interval	(2-Sided) 95%; -0.61 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.10
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1543
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0053
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.31
	Confidence Interval	(2-Sided) 95%; -0.53 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6445
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1439
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 95%; -0.47 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8402
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.30 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4439
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.11
	Confidence Interval	(2-Sided) 95%; -0.38 to 0.17
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9376
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.27 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7614
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.33 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8081
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.32 to 0.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8078
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.04
	Confidence Interval	(2-Sided) 95%; -0.25 to 0.33
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9705
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -0.28 to 0.29
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Multiple imputation method was applied for missing data, with imputation dependent on reason for missing data. ANCOVA model for imputed datasets included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WOMAC pain when going up or down stairs and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5785
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.08
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

37. Secondary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Item: Pain When Going Up or Down Stairs at Week 64
Description	WOMAC: self-administered, disease-specific questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness and physical function in participants with OA in index joint (knee or hip). Participants answered a question: "How much pain have you had when going up or down the stairs?" Participants responded about the amount of pain they experienced when going up or down stairs by using a NRS of 0 (no pain) to 10 (extreme pain), where higher scores indicated higher pain.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	7.89 (1.24)	7.88 (1.29)	7.83 (1.19)
Change at Week 64	-3.28 (2.67)	-2.97 (2.69)	-3.70 (2.50)

38. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Weeks 16, 24 and 56
Description	WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time Frame	Weeks 16, 24 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Change at Week 16: Percent Work Time Missed	-2.33 (0.62)	-3.35 (0.64)	-2.92 (0.63)
Change at Week 16:Percent Impairment While Working	-28.07 (1.58)	-26.94 (1.61)	-26.59 (1.60)
Change at Week 16: Percent Overall Work Impairment	-28.67 (1.62)	-27.51 (1.65)	-27.04 (1.63)
Change at Week 16: Percent Activity Impairment	-30.59 (1.04)	-31.36 (1.04)	-29.38 (1.05)
Change at Week 24: Percent Work Time Missed	-2.70 (0.80)	-2.19 (0.81)	-2.73 (0.81)
Change at Week 24:Percent Impairment While Working	-25.34 (1.73)	-26.66 (1.74)	-25.15 (1.74)
Change at Week 24: Percent Overall Work Impairment	-26.05 (1.78)	-27.33 (1.80)	-25.90 (1.80)
Change at Week 24: Percent Activity Impairment	-29.88 (1.13)	-30.53 (1.13)	-29.76 (1.14)
Change at Week 56: Percent Work Time Missed	-0.12 (1.56)	-1.84 (1.47)	-0.81 (1.53)
Change at Week 56:Percent Impairment While Working	-31.49 (2.22)	-29.92 (2.12)	-34.59 (2.17)
Change at Week 56: Percent Overall Work Impairment	-31.21 (2.39)	-29.29 (2.28)	-34.26 (2.34)
Change at Week 56: Percent Activity Impairment	-34.47 (1.42)	-32.91 (1.39)	-36.17 (1.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4303
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.58
	Confidence Interval	(2-Sided) 95%; -0.87 to 2.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.74
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5656
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 95%; -1.90 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.75
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9760
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -1.78 to 1.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.92
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5678
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; -1.30 to 2.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.93
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6974
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; -2.77 to 4.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.76
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Percent Work Time Missed: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1261
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.64
	Confidence Interval	(2-Sided) 95%; -0.75 to 6.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.72
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4060
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.48
	Confidence Interval	(2-Sided) 95%; -4.96 to 2.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.78
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8480
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.34
	Confidence Interval	(2-Sided) 95%; -3.84 to 3.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.78
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9230
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 95%; -4.00 to 3.63
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.94
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4421
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.51
	Confidence Interval	(2-Sided) 95%; -5.36 to 2.34
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.96
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2049
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.10
	Confidence Interval	(2-Sided) 95%; -1.70 to 7.91
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.44
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Percent Impairment While Working: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0527
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.68
	Confidence Interval	(2-Sided) 95%; -0.05 to 9.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.40
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3699
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.63
	Confidence Interval	(2-Sided) 95%; -5.21 to 1.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.82
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7945
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.48
	Confidence Interval	(2-Sided) 95%; -4.06 to 3.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.83
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9410
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 95%; -4.13 to 3.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.03
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4860
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.43
	Confidence Interval	(2-Sided) 95%; -5.44 to 2.59
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.05
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2448
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.05
	Confidence Interval	(2-Sided) 95%; -2.10 to 8.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.62
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Percent Overall Work Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0551
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.96
	Confidence Interval	(2-Sided) 95%; -0.11 to 10.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.58
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2470
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.21
	Confidence Interval	(2-Sided) 95%; -3.26 to 0.84
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.05
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0570
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.98
	Confidence Interval	(2-Sided) 95%; -4.01 to 0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.04
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9170
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95%; -2.36 to 2.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.14
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4991
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95%; -3.00 to 1.46
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.14
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2377
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.70
	Confidence Interval	(2-Sided) 95%; -1.12 to 4.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.44
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Percent Activity Impairment: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline WPAI score and baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0238
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.26
	Confidence Interval	(2-Sided) 95%; 0.43 to 6.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.44
	Estimation Comments

39. Secondary Outcome

Title	Change From Baseline in Work Productivity and Activity Impairment Questionnaire for Osteoarthritis (WPAI:OA) Scores at Week 64
Description	WPAI is 6-question participant rated questionnaire to determine the impact of OA on absenteeism, presenteeism, work productivity, and daily activity impairment for a period of 7 days prior to a visit. It yields 4 sub-scores: work time missed (absenteeism), impairment while working (presenteeism), overall work impairment (work productivity) and activity impairment (daily activity impairment). These sub-scores are expressed as an impairment percentage (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time Frame	Baseline, Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline: Percent Work Time Missed	6.1 (15.81)	6.0 (15.56)	5.2 (14.54)
Baseline: Percent Impairment While Working	60.5 (20.39)	58.3 (20.78)	59.3 (18.97)
Baseline: Percent Overall Work Impairment	62.1 (21.02)	60.0 (21.37)	60.6 (19.78)
Baseline: Percent Activity Impairment	68.3 (14.93)	67.9 (15.83)	66.7 (15.35)
Change at Week 64: Percent Work Time Missed	-1.8 (19.35)	4.1 (21.88)	-2.1 (16.65)
Change at Week 64:Percent Impairment While Working	-24.2 (27.69)	-20.7 (29.13)	-26.5 (26.24)
Change at Week 64: Percent Overall Work Impairment	-24.5 (28.77)	-19.2 (30.54)	-27.0 (27.22)
Change at Week 64: Percent Activity Impairment	-28.7 (26.68)	-24.1 (27.80)	-32.1 (24.51)

40. Secondary Outcome

Title	Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Mobility Domain
Description	Number of participants with mobility domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
No problem in walking	26 2.6%	20 2%	23 2.3%
Slight problem in walking	203 20.3%	192 19.2%	194 19.5%
Moderate problem in walking	567 56.6%	579 58%	588 59%
Severe problem in walking	204 20.4%	202 20.2%	189 19%
Unable to walk	0 0%	2 0.2%	0 0%
No problem in walking	223 22.3%	241 24.1%	216 21.7%
Slight problem in walking	374 37.3%	411 41.2%	392 39.4%
Moderate problem in walking	318 31.7%	266 26.7%	301 30.2%
Severe problem in walking	41 4.1%	48 4.8%	44 4.4%
Unable to walk	0 0%	0 0%	3 0.3%
No problem in walking	299 29.8%	319 32%	292 29.3%
Slight problem in walking	388 38.7%	371 37.2%	412 41.4%
Moderate problem in walking	199 19.9%	196 19.6%	185 18.6%
Severe problem in walking	27 2.7%	34 3.4%	26 2.6%
Unable to walk	0 0%	0 0%	0 0%
No problem in walking	259 25.8%	261 26.2%	260 26.1%
Slight problem in walking	308 30.7%	310 31.1%	337 33.8%
Moderate problem in walking	216 21.6%	200 20%	186 18.7%
Severe problem in walking	34 3.4%	43 4.3%	29 2.9%
Unable to walk	0 0%	2 0.2%	1 0.1%
No problem in walking	217 21.7%	211 21.1%	218 21.9%
Slight problem in walking	215 21.5%	209 20.9%	217 21.8%
Moderate problem in walking	110 11%	106 10.6%	91 9.1%
Severe problem in walking	19 1.9%	27 2.7%	9 0.9%
Unable to walk	0 0%	0 0%	0 0%
No problem in walking	157 15.7%	147 14.7%	170 17.1%
Slight problem in walking	205 20.5%	166 16.6%	189 19%
Moderate problem in walking	77 7.7%	120 12%	91 9.1%
Severe problem in walking	19 1.9%	24 2.4%	9 0.9%
Unable to walk	0 0%	1 0.1%	0 0%
No problem in walking	98 9.8%	66 6.6%	107 10.7%
Slight problem in walking	156 15.6%	156 15.6%	205 20.6%
Moderate problem in walking	150 15%	151 15.1%	121 12.1%
Severe problem in walking	45 4.5%	54 5.4%	21 2.1%
Unable to walk	1 0.1%	1 0.1%	0 0%

41. Secondary Outcome

Title	Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Self-Care Domain
Description	Number of participants with self-care domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
No problems washing or dressing	251 25%	242 24.2%	270 27.1%
Slight problems washing or dressing	315 31.4%	295 29.6%	319 32%
Moderate problems washing or dressing	361 36%	389 39%	350 35.1%
Severe problems washing or dressing	73 7.3%	69 6.9%	55 5.5%
Unable to wash or dress	0 0%	0 0%	0 0%
No problems washing or dressing	551 55%	569 57%	542 54.4%
Slight problems washing or dressing	270 26.9%	261 26.2%	276 27.7%
Moderate problems washing or dressing	126 12.6%	128 12.8%	134 13.5%
Severe problems washing or dressing	8 0.8%	8 0.8%	3 0.3%
Unable to wash or dress	1 0.1%	0 0%	1 0.1%
No problems washing or dressing	610 60.9%	597 59.8%	583 58.5%
Slight problems washing or dressing	216 21.6%	231 23.1%	246 24.7%
Moderate problems washing or dressing	81 8.1%	87 8.7%	77 7.7%
Severe problems washing or dressing	6 0.6%	5 0.5%	9 0.9%
Unable to wash or dress	0 0%	0 0%	0 0%
No problems washing or dressing	504 50.3%	504 50.5%	527 52.9%
Slight problems washing or dressing	214 21.4%	200 20%	192 19.3%
Moderate problems washing or dressing	91 9.1%	102 10.2%	86 8.6%
Severe problems washing or dressing	7 0.7%	9 0.9%	8 0.8%
Unable to wash or dress	1 0.1%	1 0.1%	0 0%
No problems washing or dressing	377 37.6%	359 36%	371 37.2%
Slight problems washing or dressing	140 14%	136 13.6%	125 12.6%
Moderate problems washing or dressing	42 4.2%	54 5.4%	38 3.8%
Severe problems washing or dressing	1 0.1%	4 0.4%	1 0.1%
Unable to wash or dress	1 0.1%	0 0%	0 0%
No problems washing or dressing	305 30.4%	294 29.5%	291 29.2%
Slight problems washing or dressing	107 10.7%	115 11.5%	122 12.2%
Moderate problems washing or dressing	42 4.2%	47 4.7%	40 4%
Severe problems washing or dressing	3 0.3%	2 0.2%	5 0.5%
Unable to wash or dress	1 0.1%	0 0%	1 0.1%
No problems washing or dressing	233 23.3%	192 19.2%	264 26.5%
Slight problems washing or dressing	142 14.2%	136 13.6%	131 13.2%
Moderate problems washing or dressing	66 6.6%	89 8.9%	57 5.7%
Severe problems washing or dressing	8 0.8%	11 1.1%	2 0.2%
Unable to wash or dress	1 0.1%	0 0%	0 0%

42. Secondary Outcome

Title	Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Usual Activities Domain
Description	Number of participants with usual activities domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
No problems doing usual activities	22 2.2%	24 2.4%	38 3.8%
Slight problems doing usual activities	229 22.9%	218 21.8%	225 22.6%
Moderate problems doing usual activities	538 53.7%	551 55.2%	561 56.3%
Severe problems doing usual activities	208 20.8%	201 20.1%	169 17%
Unable to do usual activities	3 0.3%	1 0.1%	1 0.1%
No problems doing usual activities	229 22.9%	266 26.7%	221 22.2%
Slight problems doing usual activities	402 40.1%	411 41.2%	426 42.8%
Moderate problems doing usual activities	292 29.1%	256 25.7%	274 27.5%
Severe problems doing usual activities	33 3.3%	31 3.1%	35 3.5%
Unable to do usual activities	0 0%	2 0.2%	0 0%
No problems doing usual activities	302 30.1%	333 33.4%	310 31.1%
Slight problems doing usual activities	402 40.1%	382 38.3%	408 41%
Moderate problems doing usual activities	184 18.4%	182 18.2%	172 17.3%
Severe problems doing usual activities	24 2.4%	21 2.1%	24 2.4%
Unable to do usual activities	1 0.1%	2 0.2%	1 0.1%
No problems doing usual activities	262 26.1%	290 29.1%	273 27.4%
Slight problems doing usual activities	353 35.2%	315 31.6%	344 34.5%
Moderate problems doing usual activities	174 17.4%	182 18.2%	166 16.7%
Severe problems doing usual activities	27 2.7%	27 2.7%	29 2.9%
Unable to do usual activities	1 0.1%	2 0.2%	1 0.1%
No problems doing usual activities	225 22.5%	221 22.1%	218 21.9%
Slight problems doing usual activities	239 23.9%	213 21.3%	233 23.4%
Moderate problems doing usual activities	85 8.5%	97 9.7%	74 7.4%
Severe problems doing usual activities	12 1.2%	20 2%	10 1%
Unable to do usual activities	0 0%	2 0.2%	0 0%
No problems doing usual activities	155 15.5%	170 17%	182 18.3%
Slight problems doing usual activities	211 21.1%	179 17.9%	199 20%
Moderate problems doing usual activities	79 7.9%	86 8.6%	69 6.9%
Severe problems doing usual activities	13 1.3%	22 2.2%	9 0.9%
Unable to do usual activities	0 0%	1 0.1%	0 0%
No problems doing usual activities	101 10.1%	69 6.9%	129 13%
Slight problems doing usual activities	173 17.3%	163 16.3%	197 19.8%
Moderate problems doing usual activities	138 13.8%	155 15.5%	115 11.5%
Severe problems doing usual activities	37 3.7%	37 3.7%	12 1.2%
Unable to do usual activities	1 0.1%	4 0.4%	1 0.1%

43. Secondary Outcome

Title	Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Pain/Discomfort Domain
Description	Number of participants with pain/discomfort domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
No pain or discomfort	6 0.6%	4 0.4%	5 0.5%
Slight pain or discomfort	81 8.1%	75 7.5%	86 8.6%
Moderate pain or discomfort	548 54.7%	574 57.5%	588 59%
Severe pain or discomfort	334 33.3%	314 31.5%	295 29.6%
Extreme pain or discomfort	31 3.1%	28 2.8%	20 2%
No pain or discomfort	82 8.2%	102 10.2%	83 8.3%
Slight pain or discomfort	433 43.2%	465 46.6%	434 43.6%
Moderate pain or discomfort	369 36.8%	327 32.8%	365 36.6%
Severe pain or discomfort	68 6.8%	68 6.8%	71 7.1%
Extreme pain or discomfort	4 0.4%	4 0.4%	3 0.3%
No pain or discomfort	128 12.8%	163 16.3%	131 13.2%
Slight pain or discomfort	508 50.7%	482 48.3%	515 51.7%
Moderate pain or discomfort	235 23.5%	225 22.5%	217 21.8%
Severe pain or discomfort	39 3.9%	44 4.4%	46 4.6%
Extreme pain or discomfort	3 0.3%	6 0.6%	6 0.6%
No pain or discomfort	117 11.7%	148 14.8%	130 13.1%
Slight pain or discomfort	413 41.2%	384 38.5%	413 41.5%
Moderate pain or discomfort	213 21.3%	218 21.8%	215 21.6%
Severe pain or discomfort	70 7%	62 6.2%	51 5.1%
Extreme pain or discomfort	4 0.4%	4 0.4%	4 0.4%
No pain or discomfort	97 9.7%	122 12.2%	110 11%
Slight pain or discomfort	298 29.7%	264 26.5%	308 30.9%
Moderate pain or discomfort	139 13.9%	130 13%	104 10.4%
Severe pain or discomfort	25 2.5%	30 3%	13 1.3%
Extreme pain or discomfort	2 0.2%	7 0.7%	0 0%
No pain or discomfort	76 7.6%	90 9%	85 8.5%
Slight pain or discomfort	248 24.8%	211 21.1%	259 26%
Moderate pain or discomfort	111 11.1%	128 12.8%	103 10.3%
Severe pain or discomfort	23 2.3%	26 2.6%	9 0.9%
Extreme pain or discomfort	0 0%	3 0.3%	3 0.3%
No pain or discomfort	45 4.5%	35 3.5%	62 6.2%
Slight pain or discomfort	169 16.9%	115 11.5%	191 19.2%
Moderate pain or discomfort	165 16.5%	191 19.1%	171 17.2%
Severe pain or discomfort	66 6.6%	76 7.6%	29 2.9%
Extreme pain or discomfort	5 0.5%	11 1.1%	1 0.1%

44. Secondary Outcome

Title	Number of Participants With Responses to European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L): Anxiety/ Depression Domain
Description	Number of participants with anxiety/ depression domain responses of EQ-5D-5L were provided. EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Higher scores indicated greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Not anxious or depressed	560 55.9%	570 57.1%	585 58.7%
Slightly anxious or depressed	252 25.1%	235 23.5%	236 23.7%
Moderately anxious or depressed	155 15.5%	151 15.1%	144 14.5%
Severely anxious or depressed	28 2.8%	37 3.7%	26 2.6%
Extremely anxious or depressed	5 0.5%	2 0.2%	3 0.3%
Not anxious or depressed	693 69.2%	703 70.4%	664 66.7%
Slightly anxious or depressed	189 18.9%	180 18%	206 20.7%
Moderately anxious or depressed	64 6.4%	71 7.1%	75 7.5%
Severely anxious or depressed	9 0.9%	7 0.7%	9 0.9%
Extremely anxious or depressed	1 0.1%	5 0.5%	2 0.2%
Not anxious or depressed	680 67.9%	701 70.2%	701 70.4%
Slightly anxious or depressed	170 17%	147 14.7%	151 15.2%
Moderately anxious or depressed	53 5.3%	62 6.2%	53 5.3%
Severely anxious or depressed	8 0.8%	6 0.6%	8 0.8%
Extremely anxious or depressed	2 0.2%	4 0.4%	2 0.2%
Not anxious or depressed	611 61%	606 60.7%	599 60.1%
Slightly anxious or depressed	147 14.7%	131 13.1%	144 14.5%
Moderately anxious or depressed	52 5.2%	66 6.6%	58 5.8%
Severely anxious or depressed	7 0.7%	10 1%	11 1.1%
Extremely anxious or depressed	0 0%	3 0.3%	1 0.1%
Not anxious or depressed	442 44.1%	429 43%	400 40.2%
Slightly anxious or depressed	92 9.2%	82 8.2%	107 10.7%
Moderately anxious or depressed	24 2.4%	35 3.5%	21 2.1%
Severely anxious or depressed	3 0.3%	6 0.6%	7 0.7%
Extremely anxious or depressed	0 0%	1 0.1%	0 0%
Not anxious or depressed	351 35%	330 33.1%	338 33.9%
Slightly anxious or depressed	88 8.8%	90 9%	86 8.6%
Moderately anxious or depressed	18 1.8%	33 3.3%	34 3.4%
Severely anxious or depressed	0 0%	3 0.3%	1 0.1%
Extremely anxious or depressed	1 0.1%	2 0.2%	0 0%
Not anxious or depressed	308 30.7%	275 27.6%	315 31.6%
Slightly anxious or depressed	104 10.4%	96 9.6%	100 10%
Moderately anxious or depressed	29 2.9%	46 4.6%	34 3.4%
Severely anxious or depressed	8 0.8%	9 0.9%	5 0.5%
Extremely anxious or depressed	1 0.1%	2 0.2%	0 0%

45. Secondary Outcome

Title	European Quality of Life-5 Dimensions-5 Levels (EQ-5D-5L) Overall Health Utility Score/Index Value
Description	EQ-5D-5L: standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional VAS. EQ-5D health state profile comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. Responses from the five domains were used to calculate a single utility index (the Overall health utility score) where values are less than or equal to (<=) 1. The Overall health utility score for a participant with no problems in all 5 items is 1 for all countries (except for Zimbabwe where it is 0.9), and is reduced where a participant reports greater levels of problems across the five dimensions.
Time Frame	Baseline, Weeks 8, 16, 24, 40, 56 and 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	0.61 (0.14)	0.61 (0.14)	0.62 (0.13)
Week 8	0.74 (0.12)	0.75 (0.13)	0.74 (0.13)
Week 16	0.77 (0.12)	0.78 (0.13)	0.77 (0.13)
Week 24	0.76 (0.14)	0.76 (0.15)	0.77 (0.14)
Week 40	0.79 (0.13)	0.78 (0.15)	0.80 (0.12)
Week 56	0.78 (0.12)	0.77 (0.15)	0.79 (0.12)
Week 64	0.72 (0.15)	0.69 (0.16)	0.75 (0.13)

46. Secondary Outcome

Title	Treatment Satisfaction Questionnaire Medicine Version II (TSQM v.II) Score With Effectiveness, Side Effects, Convenience, and Overall Satisfaction Responses
Description	TSQM v.II is a self-administered 11-item validated scale that quantified participant's level of satisfaction with study medication (scored on a 7-point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=dissatisfied, 4=somewhat satisfied, 5=satisfied, 6=very satisfied, 7=extremely satisfied]) and dissatisfaction with side effects (3 questions scored on 5 point Likert scale [1= extremely dissatisfied, 2=very dissatisfied, 3=somewhat dissatisfied, 4=slightly dissatisfied, 5=not at all dissatisfied] and 1 question on 2 point scale [0 =No, 1=Yes]). Participants were asked to assess their level of satisfaction taking all things into account. The 11 questions of the TSQM were used to calculate the 4 endpoints of effectiveness, side Effects, convenience and global satisfaction, each scored on a 0-100 scale with 100 being the best level of satisfaction.
Time Frame	Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	939	954	936
Week 16: Effectiveness	64.26 (1.03)	66.27 (1.02)	61.61 (1.03)
Week 16: Side Effects	68.61 (3.20)	73.32 (3.09)	71.03 (3.15)
Week 16: Convenience	75.50 (0.80)	75.78 (0.79)	73.70 (0.80)
Week 16: Global Satisfaction	70.32 (0.99)	70.69 (0.98)	67.13 (0.99)
Week 56: Effectiveness	69.79 (1.38)	67.91 (1.36)	67.64 (1.38)
Week 56: Side Effects	78.62 (5.28)	62.00 (4.88)	71.34 (5.14)
Week 56: Convenience	78.03 (1.12)	77.67 (1.10)	76.18 (1.11)
Week 56: Global Satisfaction	75.31 (1.27)	73.37 (1.25)	73.37 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Effectiveness; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0142
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.66
	Confidence Interval	(2-Sided) 95%; 0.53 to 4.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.08
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Effectiveness; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.67
	Confidence Interval	(2-Sided) 95%; 2.56 to 6.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.08
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Effectiveness; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1371
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.15
	Confidence Interval	(2-Sided) 95%; -0.69 to 4.99
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.45
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Effectiveness; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8524
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.27
	Confidence Interval	(2-Sided) 95%; -2.60 to 3.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.46
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Side Effects; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5253
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.42
	Confidence Interval	(2-Sided) 95%; -9.93 to 5.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.80
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Side Effects; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5381
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.29
	Confidence Interval	(2-Sided) 95%; -5.04 to 9.62
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.71
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Side Effects; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2694
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	7.27
	Confidence Interval	(2-Sided) 95%; -5.99 to 20.54
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.44
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Side Effects; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1349
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-9.34
	Confidence Interval	(2-Sided) 95%; -21.80 to 3.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 6.05
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Convenience; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0264
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.80
	Confidence Interval	(2-Sided) 95%; 0.21 to 3.38
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.81
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Convenience; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0098
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	2.07
	Confidence Interval	(2-Sided) 95%; 0.50 to 3.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.80
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Convenience; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0937
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.85
	Confidence Interval	(2-Sided) 95%; -0.31 to 4.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.10
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Convenience; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1838
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 95%; -0.70 to 3.67
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.11
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Global Satisfaction; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0025
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.18
	Confidence Interval	(2-Sided) 95%; 1.12 to 5.25
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.05
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Global Satisfaction; Week 16: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	3.55
	Confidence Interval	(2-Sided) 95%; 1.51 to 5.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.04
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	TSQM Global Satisfaction; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1373
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	1.94
	Confidence Interval	(2-Sided) 95%; -0.62 to 4.51
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.31
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	TSQM Global Satisfaction; Week 56: ANCOVA model included treatment, randomization stratification variables (index joint, highest Kellgren-Lawrence grade and NSAID) as fixed effects, baseline diary average pain as covariates, and study site as a random effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9960
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.01
	Confidence Interval	(2-Sided) 95%; -2.59 to 2.60
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.32
	Estimation Comments

47. Secondary Outcome

Title	Patient-Reported Treatment Impact Assessment- Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- What is The Current or Most Recent Treatment You Were Receiving for Osteoarthritis Pain Before Enrolling?
Description	The mPRTI is a self-administered questionnaire containing participant's global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant's willingness to use drug again assessment. To assess current or most recent treatment, participants responded for, 1=injectable prescription medicines, 2=prescription medicines taken by mouth, 3=surgery, 4=prescription medicines and surgery and 5=no treatment. Number of participants who responded for the specified question were reported.
Time Frame	Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Injectable prescription medicines	99 9.9%	98 9.8%	82 8.2%
Prescription medicines taken by mouth	611 61%	633 63.4%	647 65%
Surgery	7 0.7%	7 0.7%	9 0.9%
Prescription medicines and surgery	33 3.3%	28 2.8%	27 2.7%
No treatment	189 18.9%	188 18.8%	171 17.2%
Injectable prescription medicines	44 4.4%	47 4.7%	40 4%
Prescription medicines taken by mouth	307 30.6%	296 29.7%	324 32.5%
Surgery	8 0.8%	4 0.4%	2 0.2%
Prescription medicines and surgery	20 2%	18 1.8%	20 2%
No treatment	119 11.9%	122 12.2%	103 10.3%

48. Secondary Outcome

Title	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Global Preference Assessment- Overall, do You Prefer the Drug That You Received in This Study to Previous Treatment?
Description	The mPRTI is a self-administered questionnaire containing participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess preference to continue using the investigational product, participants responded using IRT on a 5 point Likert scale from 1-5, where, 1= yes, I definitely prefer the drug that I am receiving now, 2= I have a slight preference for the drug that I am receiving now, 3= I have no preference either way, 4= I have a slight preference for my previous treatment, 5= No, I definitely prefer my previous treatment. Higher scores indicate lesser preference to use the investigational product. Number of participants who responded for the specified question were reported.
Time Frame	Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" = participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Yes, definitely prefer the study drug	577 57.6%	597 59.8%	531 53.3%
Slight preference for the study drug	141 14.1%	169 16.9%	158 15.9%
No preference either way	149 14.9%	114 11.4%	164 16.5%
Slight preference for my previous treatment	28 2.8%	34 3.4%	36 3.6%
No, definitely prefer my previous treatment	44 4.4%	40 4%	47 4.7%
Yes, definitely prefer the study drug	342 34.1%	323 32.4%	302 30.3%
Slight preference for the study drug	70 7%	75 7.5%	89 8.9%
No preference either way	61 6.1%	65 6.5%	71 7.1%
Slight preference for my previous treatment	16 1.6%	16 1.6%	13 1.3%
No, definitely prefer my previous treatment	9 0.9%	8 0.8%	14 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0823
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0049
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0718
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1947
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

49. Secondary Outcome

Title	Patient Reported Treatment Impact Assessment-Modified (mPRTI) Score at Weeks 16 and 56: Participant Willingness to Use Drug Again Assessment- Willing to Use the Same Drug That You Have Received in This Study for Your Osteoarthritis Pain?
Description	The mPRTI is a self-administered questionnaire containing participant global preference assessment (to assess previous treatment and preference to continue using the investigational product) and participant willingness to use drug again assessment. To assess participant willingness to use drug again, participants responded using IRT on a 5 point likert scale from 1-5, where, 1= yes, I would definitely want to use the same drug again, 2= I might want to use the same drug again, 3= I am not sure, 4= I might not want to use the same drug again, 5= no, I definitely would not want to use the same drug again. Higher scores indicate lesser willingness to use the investigational product. Number of participants who responded for the specified question were reported.
Time Frame	Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" = participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Yes, definitely want to use the same drug again	627 62.6%	641 64.2%	560 56.2%
Might want to use the same drug again	138 13.8%	154 15.4%	169 17%
I am not sure	108 10.8%	96 9.6%	134 13.5%
Might not want to use the same drug again	19 1.9%	21 2.1%	23 2.3%
No:definitely wouldn't want to use same drug again	47 4.7%	42 4.2%	50 5%
Yes, definitely want to use the same drug again	352 35.1%	341 34.2%	310 31.1%
Might want to use the same drug again	78 7.8%	75 7.5%	97 9.7%
I am not sure	54 5.4%	46 4.6%	58 5.8%
Might not want to use the same drug again	4 0.4%	11 1.1%	12 1.2%
No:definitely wouldn't want to use same drug again	10 1%	14 1.4%	12 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0229
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0029
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0266
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1835
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

50. Secondary Outcome

Title	Number of Participants Who Withdrew Due to Lack of Efficacy
Description	Number of participants who withdrew from treatment due to lack of efficacy have been reported here.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Count of Participants [Participants]	60 6%	63 6.3%	91 9.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline diary average pain, baseline WOMAC pain score, classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.63
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	OR and 95% CI estimated from logistic regression model. Logistic regression model included baseline diary average pain, baseline WOMAC pain score, classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0187
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.48 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments

51. Secondary Outcome

Title	Time to Discontinuation Due to Lack of Efficacy
Description	Time to discontinuation due to lack of efficacy was defined as the time interval from the date of first study drug administration up to the date of discontinuation of participant from treatment due to lack of efficacy.
Time Frame	Baseline up to Week 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, 'Overall number of participants analyzed' signifies participants who discontinued from the study due to lack of efficacy.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	60	63	91
Median (Full Range) [days]	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0074
	Comments
	Method	Log Rank
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Missing data for the selected percentile(s) was due to the Kaplan-Meier estimate not reaching the level for discontinuation due to lack of efficacy.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0162
	Comments
	Method	Log Rank
	Comments

52. Secondary Outcome

Title	Number of Participants Who Took Rescue Medication During Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	In case of inadequate pain relief, acetaminophen/paracetamol up to 3000 mg per day and up to 3 days in a week between baseline and Week 16, and 3000 mg per day and up to 7 days per week between Week 16 and 64 could be taken as rescue medication. Number of participants with any use of rescue medication during the particular study week were summarized.
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Week 2	567 56.6%	548 54.9%	527 52.9%
Week 4	481 48%	437 43.8%	469 47.1%
Week 8	433 43.2%	377 37.8%	418 42%
Week 16	353 35.2%	330 33.1%	352 35.3%
Week 24	372 37.1%	358 35.9%	384 38.6%
Week 32	391 39%	380 38.1%	390 39.2%
Week 40	391 39%	388 38.9%	388 39%
Week 48	391 39%	393 39.4%	389 39.1%
Week 56	391 39%	408 40.9%	397 39.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1136
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.38
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3910
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.90 to 1.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7691
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.03
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1430
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6454
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.04
	Confidence Interval	(2-Sided) 95%; 0.87 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0561
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9056
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.82 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2919
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4976
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2425
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9242
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6621
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9977
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9762
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9718
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8219
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6936
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.80 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Odds ratio and 95%CI estimated from logistic regression model. Logistic regression model included baseline WOMAC pain subscale, baseline diary average pain, and classification variables index joint, highest Kellgren-Lawrence grade, NSAID and treatment.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5769
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.88 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

53. Secondary Outcome

Title	Number of Participants Who Took Rescue Medication During Week 64
Description	In case of inadequate pain relief, after Week 16, acetaminophen/paracetamol up to 3000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of participants with any use of rescue medication during Week 64 were summarized.
Time Frame	Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	437	417	437
Count of Participants [Participants]	251 25%	268 26.9%	215 21.6%

54. Secondary Outcome

Title	Number of Days of Rescue Medication Used During Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56
Description	In case of inadequate pain relief during the treatment period, acetaminophen/paracetamol up to 3000 mg per day and up to 3 days in a week between baseline and Week 16, and 3000 mg per day and up to 7 days per week between Week 16 and 64 could be taken as rescue medication. Number of days the participants used the rescue medication during the particular study weeks were summarized.
Time Frame	Weeks 2, 4, 8, 16, 24, 32, 40, 48 and 56

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Week 2	2.31 (0.13)	2.29 (0.13)	2.26 (0.13)
Week 4	1.80 (0.12)	1.70 (0.11)	1.86 (0.12)
Week 8	1.65 (0.12)	1.42 (0.11)	1.65 (0.12)
Week 16	1.29 (0.11)	1.25 (0.10)	1.39 (0.11)
Week 24	1.56 (0.12)	1.56 (0.13)	1.65 (0.13)
Week 32	1.67 (0.13)	1.66 (0.13)	1.78 (0.13)
Week 40	1.70 (0.13)	1.71 (0.13)	1.76 (0.13)
Week 48	1.68 (0.13)	1.76 (0.14)	1.74 (0.13)
Week 56	1.73 (0.13)	1.85 (0.14)	1.74 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7746
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8441
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6580
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2279
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9986
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.84 to 1.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0771
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.72 to 1.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.07
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4485
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.77 to 1.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.2817
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5426
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5385
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 32: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5041
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.94
	Confidence Interval	(2-Sided) 95%; 0.79 to 1.12
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 32: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4410
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.78 to 1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.08
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 40: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7426
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 40: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7469
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.97
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 48: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6784
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.96
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 48: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8822
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.85 to 1.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9119
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.83 to 1.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5148
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.06
	Confidence Interval	(2-Sided) 95%; 0.89 to 1.26
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.09
	Estimation Comments

55. Secondary Outcome

Title	Number of Days of Rescue Medication Used During Week 64
Description	In case of inadequate pain relief, after week 16, acetaminophen/paracetamol up to 3000 mg per day up to 7 days in a week could be taken as rescue medication and use was reported weekly via diary. Number of days the participants used the rescue medication during Week 64 were summarized.
Time Frame	Week 64

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed' = participants who took rescue medication.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	437	417	437
Mean (Standard Deviation) [days]	2.0 (2.38)	2.3 (2.46)	1.7 (2.26)

56. Secondary Outcome

Title	Amount of Rescue Medication Used During Weeks 2, 4, 8 and 16
Description	In case of inadequate pain relief, acetaminophen/paracetamol up to 3000 mg per day up to 3 days in a week could be taken as rescue medication. The total dosage of acetaminophen in milligrams used during the specified week were summarized.
Time Frame	Weeks 2, 4, 8 and 16

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo).

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Week 2	2880.3 (353.05)	2898.7 (358.72)	3310.5 (410.42)
Week 4	2107.8 (302.24)	1946.5 (277.29)	2814.1 (401.29)
Week 8	1995.6 (322.53)	1628.8 (258.90)	2839.7 (446.00)
Week 16	1696.4 (307.80)	1581.6 (284.12)	2320.0 (413.14)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 2: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3348
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.15
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 2: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3595
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.88
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0854
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0281
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.69
	Confidence Interval	(2-Sided) 95%; 0.50 to 0.96
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.12
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0595
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.70
	Confidence Interval	(2-Sided) 95%; 0.49 to 1.01
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0030
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.40 to 0.83
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.11
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1389
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.48 to 1.11
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.15
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Analysis was performed using negative binomial model with model terms of baseline WOMAC Pain subscale score, baseline diary average pain score, index joint, Kellgren Lawrence grade, NSAID and treatment group.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0709
	Comments
	Method	Negative binomial model
	Comments
Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	0.68
	Confidence Interval	(2-Sided) 95%; 0.45 to 1.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.14
	Estimation Comments

57. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Visits of Services Directly Related to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Visits of services directly related to OA evaluated were: visits to primary care physician, neurologist, rheumatologist, physician assistant or nurse practitioner, pain specialist, orthopedist, physical therapist, chiropractor, alternative medicine or therapy, podiatrist, nutritionist/dietitian, radiologist, home healthcare services and other practitioner.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline: Primary Care Physician	1.0	1.0	1.0
Baseline: Neurologist	1.0	1.0	1.0
Baseline: Rheumatologist	1.0	2.0	2.0
Baseline:Physician Assistant or Nurse Practitioner	1.0	1.0	1.0
Baseline: Pain Specialist	1.0	2.0	1.0
Baseline: Orthopedist	2.0	1.0	2.0
Baseline: Physical Therapist	4.0	3.0	3.0
Baseline: Chiropractor	3.0	3.0	3.0
Baseline: Alternative Medicine or Therapy	2.0	2.0	2.0
Baseline: Podiatrist	1.0	1.0	1.0
Baseline: Nutritionist/Dietitian	1.0	1.0	1.0
Baseline: Radiologist	1.0	1.0	1.0
Baseline: Home Healthcare Services	2.0	1.0	3.0
Baseline: Other Practitioner	2.0	2.0	2.0
Week 64: Primary Care Physician	1.0	1.0	1.0
Week 64: Neurologist	1.0	1.0	1.0
Week 64: Rheumatologist	1.0	1.0	1.0
Week 64: Physician Assistant Or Nurse Practitioner	1.0	1.0	2.0
Week 64: Pain Specialist	1.0	1.0	1.0
Week 64: Orthopedist	1.0	1.0	1.0
Week 64: Physical Therapist	4.0	4.5	3.0
Week 64: Chiropractor	3.0	2.0	3.0
Week 64: Alternative Medicine or Therapy	1.0	2.0	2.0
Week 64: Podiatrist	1.0	1.0	1.0
Week 64: Nutritionist/Dietitian	2.0	1.0	1.0
Week 64: Radiologist	1.0	1.0	1.0
Week 64: Home Healthcare Services	4.0	4.0	5.0
Week 64: Other Practitioner	1.0	1.0	1.0
Week 80: Primary Care Physician	1.0	1.0	1.0
Week 80: Neurologist	1.0	1.0	1.0
Week 80: Rheumatologist	1.0	1.0	1.0
Week 80: Physician Assistant or Nurse Practitioner	1.0	1.0	1.0
Week 80: Pain Specialist	1.5	2.0	1.0
Week 80: Orthopedist	1.5	1.0	1.0
Week 80: Physical Therapist	8.0	5.5	3.0
Week 80: Chiropractor	3.0	4.5	3.0
Week 80: Alternative Medicine or Therapy	3.5	1.0	2.0
Week 80: Podiatrist	1.0	1.0	3.0
Week 80: Nutritionist/Dietitian	1.0	1.5	1.0
Week 80: Radiologist	1.0	1.0	1.0
Week 80: Home Healthcare Services	2.5	4.0	1.0
Week 80: Other Practitioner	1.0	1.0	1.0

58. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Participants Who Visited the Emergency Room Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who visited the emergency room due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	15 1.5%	23 2.3%	11 1.1%
Week 64	10 1%	15 1.5%	5 0.5%
Week 80	4 0.4%	5 0.5%	2 0.2%

59. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Visits to the Emergency Room Due to Osteoarthritis
Description	Osteoarthritis HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of visits to the emergency room due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	15	23	11
Baseline	1.0	1.0	1.0
Week 64	1.0	1.0	1.0
Week 80	1.0	3.0	1.0

60. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Participants Hospitalized Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who were hospitalized due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	11 1.1%	6 0.6%	1 0.1%
Week 64	5 0.5%	11 1.1%	6 0.6%
Week 80	8 0.8%	12 1.2%	0 0%

61. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Nights Stayed in the Hospital Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of nights stayed in the hospital due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	11	12	6
Baseline	12.0	9.0	11.0
Week 64	2.0	2.0	2.0
Week 80	2.0	2.0

62. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Participants Who Used Any Aids/Devices for Doing Things Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who used any aids/devices for doing things. Aids such as walking aid, wheelchair, device or utensil for dress/bathe/eat and any other aids/devices.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Never	852 85%	838 84%	851 85.4%
Rarely	27 2.7%	18 1.8%	24 2.4%
Sometimes	71 7.1%	69 6.9%	75 7.5%
Often	32 3.2%	43 4.3%	26 2.6%
Always	19 1.9%	29 2.9%	19 1.9%
Never	992 99%	989 99.1%	988 99.2%
Rarely	2 0.2%	2 0.2%	1 0.1%
Sometimes	4 0.4%	6 0.6%	5 0.5%
Often	3 0.3%	0 0%	1 0.1%
Always	0 0%	0 0%	0 0%
Never	970 96.8%	976 97.8%	977 98.1%
Rarely	2 0.2%	1 0.1%	0 0%
Sometimes	7 0.7%	6 0.6%	6 0.6%
Often	16 1.6%	9 0.9%	7 0.7%
Always	6 0.6%	5 0.5%	5 0.5%
Never	932 93%	935 93.7%	921 92.5%
Rarely	8 0.8%	7 0.7%	9 0.9%
Sometimes	27 2.7%	22 2.2%	41 4.1%
Often	27 2.7%	22 2.2%	14 1.4%
Always	7 0.7%	11 1.1%	10 1%
Never	662 66.1%	662 66.3%	714 71.7%
Rarely	21 2.1%	9 0.9%	12 1.2%
Sometimes	48 4.8%	47 4.7%	37 3.7%
Often	20 2%	30 3%	17 1.7%
Always	22 2.2%	34 3.4%	19 1.9%
Never	765 76.3%	776 77.8%	794 79.7%
Rarely	2 0.2%	1 0.1%	2 0.2%
Sometimes	4 0.4%	2 0.2%	3 0.3%
Often	2 0.2%	1 0.1%	0 0%
Always	0 0%	2 0.2%	0 0%
Never	760 75.8%	768 77%	792 79.5%
Rarely	2 0.2%	1 0.1%	1 0.1%
Sometimes	7 0.7%	7 0.7%	2 0.2%
Often	3 0.3%	5 0.5%	2 0.2%
Always	1 0.1%	1 0.1%	2 0.2%
Never	733 73.2%	720 72.1%	771 77.4%
Rarely	6 0.6%	9 0.9%	11 1.1%
Sometimes	19 1.9%	26 2.6%	8 0.8%
Often	12 1.2%	20 2%	6 0.6%
Always	3 0.3%	7 0.7%	3 0.3%
Never	373 37.2%	322 32.3%	386 38.8%
Rarely	12 1.2%	10 1%	6 0.6%
Sometimes	25 2.5%	25 2.5%	17 1.7%
Often	14 1.4%	17 1.7%	7 0.7%
Always	8 0.8%	22 2.2%	8 0.8%
Never	430 42.9%	389 39%	421 42.3%
Rarely	0 0%	2 0.2%	2 0.2%
Sometimes	1 0.1%	4 0.4%	1 0.1%
Often	0 0%	0 0%	0 0%
Always	1 0.1%	1 0.1%	0 0%
Never	425 42.4%	383 38.4%	422 42.4%
Rarely	0 0%	0 0%	1 0.1%
Sometimes	2 0.2%	6 0.6%	1 0.1%
Often	3 0.3%	5 0.5%	0 0%
Always	2 0.2%	2 0.2%	0 0%
Never	416 41.5%	375 37.6%	410 41.2%
Rarely	4 0.4%	3 0.3%	4 0.4%
Sometimes	5 0.5%	11 1.1%	4 0.4%
Often	5 0.5%	4 0.4%	2 0.2%
Always	2 0.2%	3 0.3%	4 0.4%

63. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Number of Participants Who Quit Job Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was number of participants who quit job due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either tanezumab or matching placebo). Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	995
Baseline	47 4.7%	55 5.5%	65 6.5%
Week 64	28 2.8%	35 3.5%	26 2.6%
Week 80	12 1.2%	18 1.8%	6 0.6%

64. Secondary Outcome

Title	Health Care Resource Utilization (HCRU): Duration Since Quitting Job Due to Osteoarthritis
Description	OA HCRU assessed healthcare usage during the last 3 months (for Baseline and Week 80) and past 8 weeks (for Week 64). Domain evaluated was duration since quitting job due to OA.
Time Frame	Baseline, Weeks 64 and 80

Outcome Measure Data

Analysis Population Description

ITT population was analyzed. One additional participant apart from the ones who had responded for quitting job responded to duration since quitting job. Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	47	55	66
Baseline	2.0	1.8	2.4
Week 64	2.4	1.8	4.0
Week 80	2.0	2.0	1.8

65. Secondary Outcome

Title	Number of Participants With Categorical Change From Baseline in Lower Extremity Activity Scale (LEAS) at Weeks 4, 8, 16, 24, 56 and 80
Description	The LEAS is a self-administered scale to assess activity level in participants having total knee arthroplasty. The LEAS scale reflected four levels of lower-extremity activity (1)housebound(unable to walk or a minimal ability to walk) (2)more ordinary walking about the house (3)walking about the community (4)walking about the community as well as substantial work or exercise. It consisted of 12 questions resulting in 18-level scale that allowed participants to select a single description that most represented his or her self-perceived activity level. The final score was simply the number of the descriptor selected by the participant as being most representative of his or her activity level. The minimum possible score was 1(entirely bedbound) and the maximum possible score was 18(currently competitive athlete). Higher score indicated increased activity. Categorical changes from baseline were reported in terms of improvement (Change >0), No change and worsening (Change less than [<] 0).
Time Frame	Baseline, Weeks 4, 8, 16, 24, 56 and 80

Outcome Measure Data

Analysis Population Description

ITT population included all randomized participants who received at least one dose of SC study medication (either Tanezumab or matching placebo). Here 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Improvement	423 42.2%	421 42.2%	411 41.3%
No Change	370 36.9%	394 39.5%	369 37%
Worsening	207 20.7%	180 18%	214 21.5%
Improvement	454 45.3%	443 44.4%	445 44.7%
No Change	325 32.4%	362 36.3%	348 34.9%
Worsening	221 22.1%	190 19%	201 20.2%
Improvement	488 48.7%	470 47.1%	477 47.9%
No Change	288 28.7%	312 31.3%	312 31.3%
Worsening	224 22.4%	213 21.3%	205 20.6%
Improvement	478 47.7%	458 45.9%	467 46.9%
No Change	277 27.6%	302 30.3%	291 29.2%
Worsening	245 24.5%	235 23.5%	236 23.7%
Improvement	486 48.5%	429 43%	461 46.3%
No Change	270 26.9%	314 31.5%	300 30.1%
Worsening	244 24.4%	252 25.3%	233 23.4%
Improvement	220 22%	196 19.6%	227 22.8%
No Change	105 10.5%	97 9.7%	125 12.6%
Worsening	113 11.3%	115 11.5%	80 8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 4: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6037
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 4: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1928
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 8: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7204
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 8: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7969
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7857
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 16: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6627
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 24: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9867
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 24: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.8190
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 2.5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7284
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Tanezumab 5 mg, NSAID
	Comments	Week 56: Cochran-Mantel-Haenszel test for row mean scores differ, stratified by the combinations of the three stratification factors (index joint, highest Kellgren-Lawrence grade and NSAID)
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1545
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

66. Secondary Outcome

Title	Change From Baseline in Average Daily Minutes of Physical Activity at Weeks 16 and 56
Description	Participant activity level was assessed using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).
Time Frame	Baseline, Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

Accelerometry analysis set = All participants treated with tanezumab or matching placebo SC who had any baseline or post-baseline accelerometry data. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	36	46	44
Baseline	97.0	107.1	99.2
Change at Week 16	3.9	2.9	-4.2
Change at Week 56	-8.9	-10.1	3.9

67. Secondary Outcome

Title	Change From Baseline in Average Daily Physical Activity Counts at Weeks 16 and 56
Description	An average daily physical activity count was measured using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).
Time Frame	Baseline, Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

Accelerometry analysis set = All participants treated with tanezumab or matching placebo SC who had any baseline or post-baseline accelerometry data. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	36	46	44
Baseline	75244	95911	74414
Change at Week 16	-470.0	-2261	1202.9
Change at Week 56	-14552	-8313	4414.3

68. Secondary Outcome

Title	Change From Baseline in Average Daily Minutes of Moderate to Vigorous Physical Activity at Weeks 16 and 56
Description	An average daily physical activity count was measured using actigraphy which was then sorted into three intensity thresholds: light (100 - less than {<1500} counts moderate (1,500 - <6500 counts), and vigorous (>=6500 counts). Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).
Time Frame	Baseline, Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

Accelerometry analysis set = All participants treated with tanezumab or matching placebo SC who had any baseline or post-baseline accelerometry data. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	36	46	44
Baseline	41.2	53.1	41.9
Change at Week 16	0.7	-1.6	-0.1
Change at Week 56	-3.8	2.7	7.4

69. Secondary Outcome

Title	Change From Baseline in Average Daily Minutes of Bouted (Sustained) Moderate to Vigorous Physical Activity at Weeks 16 and 56
Description	An average daily physical activity count was measured using actigraphy which was then sorted into three intensity thresholds: light (100 - <1,500 counts) moderate (1,500 - <6,500 counts), and vigorous (>=6,500 counts). Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).A "bout" of moderate to vigorous activity was defined as 10 or more consecutive minutes above the moderate physical activity level threshold, with allowance for interruptions of 1 or 2 minutes below the threshold.
Time Frame	Baseline, Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

Accelerometry analysis set = All participants treated with tanezumab or matching placebo SC who had any baseline or post-baseline accelerometry data. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	36	46	44
Baseline	0.0	0.0	0.0
Change at Week 16	0.0	0.0	0.0
Change at Week 56	0.0	-1.4	0.0

70. Secondary Outcome

Title	Change From Baseline in Average Daily Step Count at Weeks 16 and 56
Description	Average daily step count was measured using actigraphy. Participants continuously wore the accelerometer (apart for water activities) in the morning until going to bed at night for 7 or 14 consecutive days while going about their usual daily activities. Participants maintained a log (electronic or written) to record when the accelerometer was put on in the morning and removed at night (or if removed for any other purpose).
Time Frame	Baseline, Weeks 16 and 56

Outcome Measure Data

Analysis Population Description

Accelerometry analysis set = All participants treated with tanezumab or matching placebo SC who had any baseline or post-baseline accelerometry data. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	36	46	44
Baseline	4851.0	5834.8	4779.0
Change at Week 16	350.9	87.8	-705.7
Change at Week 56	-1938	-543.2	242.6

71. Secondary Outcome

Title	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 80 that were absent before treatment or that worsened relative to pre-treatment state. AEs included both serious and non-serious AEs. Clinically significant physical examination abnormalities were reported as AEs.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
AEs	681 68%	744 74.5%	666 66.9%
SAEs	78 7.8%	110 11%	66 6.6%

72. Secondary Outcome

Title	Number of Participants With Treatment-Related Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to Week 80 that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Treatment Related AEs	190 19%	250 25.1%	179 18%
Treatment Related SAEs	7 0.7%	20 2%	7 0.7%

73. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities With Regard to Normal Baseline
Description	Primary Abnormality criteria: HGB, hematocrit, RBC count <0.8* lower limit of normal(LLN); Ery. mean corpuscular volume/hemoglobin/ HGB concentration, RBCs distribution width <0.9*LLN, >1.1*upper limit of normal(ULN); platelets <0.5*LLN,>1.75*ULN; Leukocytes <0.6*LLN, >1.5*ULN; Lymphocytes, Neutrophils <0.8*LLN, >1.2*ULN; Basophils,Eosinophils,Monocytes>1.2*ULN; Prothrombin time/Intl. normalized ratio>1.1*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase,alanine aminotransferase,gamma GT,LDH,alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen,creatinine,Cholesterol,triglycerides >1.3*ULN; Urate>1.2*ULN; sodium<0.95*LLN,>1.05*ULN; potassium,chloride,calcium,magnesium,bicarbonate <0.9*LLN, >1.1*ULN; phosphate<0.8*LLN, >1.2*ULN; glucose<0.6*LLN, >1.5*ULN; HGB A1C >1.3*ULN; creatine kinase>2.0*ULN, specific gravity<1.003, >1.030; pH<4.5, >8;Urine erythrocytes,Leukocytes>=20.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	877	897	884
Count of Participants [Participants]	109 10.9%	102 10.2%	121 12.1%

74. Secondary Outcome

Title	Number of Participants With Laboratory Test Abnormalities With Regard to Abnormal Baseline
Description	Primary Abnormality criteria: hemoglobin; hematocrit; RBC count < 0.8*LLN; Ery. mean corpuscular volume/ hemoglobin/ HGB concentration, erythrocytes distribution width <0.9*LLN, >1.1*ULN; platelets <0.5*LLN,>1.75*upper limit of normal (ULN); white blood cell count<0.6*LLN, >1.5*ULN; Lymphocytes, Lymphocytes/Leukocytes, Neutrophils, Neutrophils/Leukocytes <0.8*LLN, >1.2*ULN; Basophils, Eosinophils, Monocytes >1.2*ULN; total bilirubin>1.5*ULN; aspartate aminotransferase, alanine aminotransferase, gamma GT,LDH, alkaline phosphatase >3.0*ULN; total protein; albumin<0.8*LLN, >1.2*ULN; blood urea nitrogen, creatinine, Cholesterol, triglycerides >1.3*ULN; Urate >1.2*ULN; sodium <0.95*LLN,>1.05*ULN; potassium, chloride, calcium, magnesium, bicarbonate <0.9*LLN, >1.1*ULN; phosphate <0.8*LLN, >1.2*ULN; glucose <0.6*LLN, >1.5*ULN; Hemoglobin A1C >1.3*ULN; creatine kinase >2.0*ULN; specific gravity<1.003, >1.030; Urine erythrocytes,Leukocytes>=20; Hyaline Casts>=1.
Time Frame	Baseline up to Week 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here 'Overall number of participants analyzed' = participants who were evaluable for this outcome measure.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	706	731	691
Count of Participants [Participants]	78 7.8%	61 6.1%	84 8.4%

75. Secondary Outcome

Title	Change From Baseline in Blood Pressure (BP) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Description	Measurement of BP included sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here, "Number analyzed" signifies those participants who were evaluable for this outcome measure for specified categories.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
SBP: Baseline	128.9 (12.91)	129.3 (13.43)	128.8 (13.26)
SBP: Change at Week 2	-2.7 (11.69)	-4.2 (11.92)	-1.2 (11.24)
SBP: Change at Week 4	-4.0 (11.44)	-4.9 (12.68)	-1.8 (11.29)
SBP: Change at Week 8	-2.9 (12.16)	-3.8 (12.60)	-1.8 (11.68)
SBP: Change at Week 16	-3.0 (11.66)	-3.7 (12.95)	-1.3 (12.37)
SBP: Change at Week 24	-3.0 (12.35)	-3.1 (13.49)	-1.7 (11.83)
SBP: Change at Week 32	-2.8 (11.95)	-3.3 (13.70)	-1.7 (13.49)
SBP: Change at Week 40	-2.5 (11.35)	-3.8 (14.41)	-2.3 (13.42)
SBP: Change at Week 48	-2.7 (12.21)	-3.0 (13.29)	-2.2 (12.97)
SBP: Change at Week 56	-3.1 (11.76)	-3.4 (13.78)	-2.2 (12.64)
SBP: Change at Week 64	-2.1 (13.40)	-2.1 (13.56)	-2.8 (13.33)
SBP: Change at Week 80	-1.0 (13.24)	-1.3 (13.71)	-2.3 (13.31)
DBP: Baseline	79.3 (8.56)	79.1 (8.68)	79.3 (8.57)
DBP: Change at Week 2	-1.3 (8.29)	-2.1 (7.96)	-1.1 (7.84)
DBP: Change at Week 4	-2.2 (8.06)	-2.5 (8.10)	-1.4 (8.19)
DBP: Change at Week 8	-1.1 (7.84)	-1.7 (8.24)	-1.1 (8.23)
DBP: Change at Week 16	-1.3 (8.14)	-1.8 (8.53)	-1.1 (8.30)
DBP: Change at Week 24	-1.3 (8.39)	-1.7 (8.91)	-1.4 (8.26)
DBP: Change at Week 32	-1.3 (8.28)	-1.4 (9.14)	-1.2 (8.91)
DBP: Change at Week 40	-1.2 (8.07)	-2.0 (8.90)	-1.1 (8.69)
DBP: Change at Week 48	-0.9 (8.82)	-1.8 (8.89)	-1.5 (8.65)
DBP: Change at Week 56	-1.8 (8.61)	-1.9 (9.11)	-1.2 (8.69)
DBP: Change at Week 64	-0.8 (8.63)	-0.8 (9.23)	-1.7 (9.03)
DBP: Change at Week 80	-0.6 (8.73)	-0.6 (9.66)	-1.2 (9.35)

76. Secondary Outcome

Title	Change From Baseline in Heart Rate at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Description	Heart rate (pulse rate) was measured at sitting position.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	998	996
Baseline	70.8 (9.09)	70.5 (9.66)	70.6 (9.36)
Change at Week 2	1.8 (8.65)	2.0 (8.50)	1.1 (8.31)
Change at Week 4	1.6 (9.00)	2.0 (9.03)	1.2 (8.75)
Change at Week 8	0.7 (9.06)	0.8 (8.54)	0.1 (8.78)
Change at Week 16	0.5 (9.37)	0.5 (9.14)	0.8 (8.86)
Change at Week 24	0.4 (9.46)	0.7 (9.36)	0.8 (9.24)
Change at Week 32	1.2 (9.67)	1.6 (9.34)	1.7 (9.70)
Change at Week 40	1.2 (9.89)	1.6 (9.40)	1.4 (8.71)
Change at Week 48	0.6 (9.86)	1.0 (9.34)	1.3 (9.44)
Change at Week 56	0.2 (9.51)	0.1 (10.15)	-0.0 (9.28)
Change at Week 64	1.5 (9.81)	1.5 (9.55)	0.5 (9.84)
Change at Week 80	0.9 (10.24)	0.6 (9.97)	0.9 (9.61)

77. Secondary Outcome

Title	Change From Baseline in Electrocardiogram (ECG) Parameters at Weeks 56 and 80
Description	A 12-lead ECG was recorded after participants had rested for at least 5 minutes in the supine position in a quiet environment. All standard intervals (PR, QRS, QT, QTcF, QTcB, RR intervals) were collected. ECG abnormalities included: 1) QT interval, QT interval corrected using Bazett's formula (QTcB) and QT interval corrected using Fridericia's formula (QTcF): increase from baseline greater than (>) 30 millisecond (ms) or 60 ms; absolute value > 450 ms, >480 ms and > 500 ms; 2) heart rate (HR) : absolute value <=50 bpm and decrease from baseline >=20 bpm; absolute value >=120 beats per minute (bpm) and increase from baseline >=20 bpm; 3) PR interval: absolute value >=220 ms and increase from baseline >=20 ms; 4) QRS interval: absolute value >= 120 ms.
Time Frame	Baseline, Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	995	995
RR Interval: Baseline	940.5 (136.21)	940.1 (144.48)	936.1 (142.31)
RR Interval:Change at Week 56	-26.3 (123.23)	-22.6 (128.58)	-14.9 (128.73)
RR Interval:Change at Week 80	-33.6 (119.23)	-32.4 (126.08)	-34.3 (133.83)
PR Interval: Baseline	165.0 (27.43)	165.9 (25.45)	163.9 (23.98)
PR Interval:Change at Week 56	1.7 (12.98)	0.6 (13.33)	1.7 (14.40)
PR Interval:Change at Week 80	0.3 (13.39)	-0.8 (14.70)	0.6 (13.80)
QRS Interval: Baseline	94.9 (13.12)	94.6 (13.65)	94.3 (13.16)
QRS Interval:Change at Week 56	0.2 (8.22)	0.4 (8.30)	-0.4 (7.39)
QRS Interval:Change at Week 80	-0.2 (8.12)	1.0 (8.64)	-0.1 (7.81)
QT Interval: Baseline	405.0 (28.86)	403.8 (30.08)	404.3 (29.33)
QT Interval:Change at Week 56	-3.5 (24.07)	-4.5 (25.06)	-2.9 (26.58)
QT Interval:Change at Week 80	-6.2 (22.56)	-6.8 (24.46)	-6.0 (25.34)
QTCB Interval: Baseline	419.3 (21.85)	418.5 (21.96)	419.7 (21.60)
QTCB Interval:Change at Week 56	2.3 (18.82)	0.5 (17.83)	0.2 (19.66)
QTCB Interval:Change at Week 80	1.5 (19.37)	0.2 (17.98)	1.7 (19.06)
QTCF Interval: Baseline	414.2 (19.96)	413.3 (20.09)	414.3 (19.49)
QTCF Interval:Change at Week 56	0.3 (16.24)	-1.2 (15.55)	-0.8 (17.50)
QTCF Interval:Change at Week 80	-1.2 (16.16)	-2.1 (15.55)	-1.0 (16.21)

78. Secondary Outcome

Title	Change From Baseline in Heart Rate (as Assessed by ECG) at Weeks 56 and 80
Description	Heart rate was measured at sitting position.
Time Frame	Baseline, Weeks 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1002	995	995
Baseline	65.2 (9.70)	65.4 (10.30)	65.6 (10.36)
Change at Week 56	2.0 (9.10)	1.7 (9.72)	1.0 (9.95)
Change at Week 80	2.7 (9.00)	2.3 (9.34)	2.5 (10.02)

79. Secondary Outcome

Title	Number of Participants With Confirmed Orthostatic Hypotension
Description	Orthostatic hypotension was defined as postural change (supine to standing) that met the following criteria: For systolic BP <=150 mmHg (mean supine): Reduction in systolic BP>=20 mmHg or reduction in diastolic BP>=10 mmHg at the 1 and/or 3 minute standing BP measurements. For systolic BP >150 mmHg (mean supine): Reduction in systolic BP>=30 mmHg or reduction in diastolic BP>=15 mmHg at the 1 and/or 3 minute standing BP measurements. If the 1 minute or 3 minute standing BP in a sequence met the orthostatic hypotension criteria, then that sequence was considered positive. If 2 of 2 or 2 of 3 sequences were positive, then orthostatic hypotension was considered confirmed.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1001	996	996
Baseline	0 0%	3 0.3%	1 0.1%
Week 2	2 0.2%	4 0.4%	2 0.2%
Week 4	1 0.1%	1 0.1%	2 0.2%
Week 8	0 0%	2 0.2%	1 0.1%
Week 16	1 0.1%	1 0.1%	0 0%
Week 24	0 0%	1 0.1%	1 0.1%
Week 32	2 0.2%	2 0.2%	0 0%
Week 40	1 0.1%	1 0.1%	1 0.1%
Week 48	2 0.2%	2 0.2%	0 0%
Week 56	1 0.1%	1 0.1%	1 0.1%
Week 64	0 0%	1 0.1%	3 0.3%
Week 80	0 0%	1 0.1%	0 0%

80. Secondary Outcome

Title	Change From Baseline in Survey of Autonomic Symptom (SAS) Scores at Weeks 24, 56 and 80
Description	The SAS is a 12 item (11 for females) questionnaire, from which the total number of symptoms (0-12 for males and 0-11 for females) is calculated. Each positive symptom is rated from 1 (not at all) to 5 (a lot). The total impact score was the sum of all symptom rating scores, with 0 assigned where the participant did not have the particular symptom. The range for the total impact score is 0-60 for males and 0-55 for females, higher scores indicating higher impact.
Time Frame	Baseline, Weeks 24, 56 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	997	996
Number of symptoms reported: Baseline	0.47 (0.76)	0.53 (0.78)	0.49 (0.76)
Number of symptoms reported: Change at Week 24	0.21 (1.13)	0.18 (1.22)	0.11 (1.20)
Number of symptoms reported: Change at Week 56	0.28 (1.19)	0.33 (1.34)	0.22 (1.21)
Number of symptoms reported: Change at Week 80	0.89 (1.39)	0.94 (1.43)	0.74 (1.22)
Total symptom impact score: Baseline	1.10 (1.84)	1.23 (1.89)	1.13 (1.82)
Total symptom impact score: Change at Week 24	0.66 (2.90)	0.52 (3.19)	0.33 (2.99)
Total symptom impact score: Change at Week 56	0.97 (3.29)	1.21 (4.01)	0.82 (3.40)
Total symptom impact score: Change at Week 80	1.33 (3.85)	1.31 (4.36)	0.89 (3.65)

81. Secondary Outcome

Title	Change From Baseline in Neuropathy Impairment Score (NIS) at Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80
Description	NIS is a standardized instrument used to evaluate participant for signs of peripheral neuropathy. NIS is the sum of scores of 37 items, from both the left and right side, where 24 items scored from 0 (normal) to 4 (paralysis), higher score indicated higher abnormality/impairment and 13 items scored from 0 (normal), 1 (decreased) and 2 (absent), higher score indicated higher impairment. NIS possible overall score ranged from 0 (no impairment) to 244 (maximum impairment), higher scores indicated increased impairment.
Time Frame	Baseline, Weeks 2, 4, 8, 16, 24, 32, 40, 48, 56, 64 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. 'Overall number of participants analyzed'=participants evaluable for this outcome measure. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg	NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.	Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
Measure Participants	1000	995	994
Baseline	1.85 (4.30)	1.70 (4.45)	1.87 (4.47)
Change at Week 2	-0.22 (2.15)	-0.13 (1.40)	-0.15 (1.67)
Change at Week 4	-0.16 (2.06)	-0.17 (1.92)	-0.19 (2.32)
Change at Week 8	-0.27 (2.28)	-0.22 (2.08)	-0.36 (2.55)
Change at Week 16	-0.27 (2.32)	-0.31 (2.48)	-0.47 (3.06)
Change at Week 24	-0.32 (2.39)	-0.35 (2.76)	-0.49 (3.08)
Change at Week 32	-0.37 (2.46)	-0.40 (2.75)	-0.53 (3.17)
Change at Week 40	-0.35 (2.42)	-0.43 (2.80)	-0.53 (3.32)
Change at Week 48	-0.37 (2.46)	-0.49 (3.13)	-0.55 (3.21)
Change at Week 56	-0.35 (2.48)	-0.52 (3.26)	-0.58 (3.22)
Change at Week 64	-0.32 (2.60)	-0.47 (3.24)	-0.57 (3.20)
Change at Week 80	-0.35 (2.53)	-0.47 (3.35)	-0.62 (3.28)

82. Secondary Outcome

Title	Number of Participants With Anti-Tanezumab Antibodies
Description	Human serum anti-drug antibody (ADA) samples were analyzed for the presence or absence of anti-tanezumab antibodies by using a semi quantitative enzyme linked immunosorbent assay (ELISA).
Time Frame	Baseline, Weeks 8, 16, 32, 48, 56, 64 and 80

Outcome Measure Data

Analysis Population Description

Safety population included all participants treated with tanezumab or placebo SC. Here, "Number analyzed" =participants who were evaluable at specified time point for each arm, respectively.

Arm/Group Title	Tanezumab 2.5 mg	Tanezumab 5 mg
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.	Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.
Measure Participants	1002	998
Baseline	116 11.6%	83 8.3%
Week 8	120 12%	93 9.3%
Week 16	98 9.8%	83 8.3%
Week 32	108 10.8%	81 8.1%
Week 48	96 9.6%	78 7.8%
Week 56	82 8.2%	66 6.6%
Week 64	69 6.9%	60 6%
Week 80	50 5%	42 4.2%

Adverse Events

Time Frame	Baseline up to Week 56
Adverse Event Reporting Description	Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Analysis performed on safety set.
Arm/Group Title	Tanezumab 2.5 mg		Tanezumab 5 mg		NSAID
Arm/Group Description	Tanezumab (RN624 or PF-04383119) 2.5 milligram (mg) injection administered subcutaneously (SC) once every 8 weeks, from Baseline (Day 1) up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac extended release (ER), twice daily, from Baseline up to Week 56.		Tanezumab (RN624 or PF-04383119) 5 mg injection administered SC once every 8 weeks, from Baseline up to Week 48 and oral placebo tablets matched to naproxen, celecoxib or diclofenac ER, twice daily, from Baseline up to week 56.		Non-steroidal anti-inflammatory drug (NSAID) tablets (naproxen 500 mg, celecoxib 100 mg, or diclofenac ER 75 mg), administered orally, twice daily, from Baseline up to week 56 and placebo matched to tanezumab (RN624 or PF-04383119) injection administered SC once every 8 weeks, from Baseline up to Week 48.
All Cause Mortality
	Tanezumab 2.5 mg		Tanezumab 5 mg		NSAID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/1002 (0.4%)		5/998 (0.5%)		1/996 (0.1%)
Serious Adverse Events
	Tanezumab 2.5 mg		Tanezumab 5 mg		NSAID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/1002 (5.1%)		80/998 (8%)		46/996 (4.6%)
Blood and lymphatic system disorders
Anaemia	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Cardiac disorders
Acute myocardial infarction	1/1002 (0.1%)		1/998 (0.1%)		3/996 (0.3%)
Aortic valve incompetence	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Atrial fibrillation	1/1002 (0.1%)		1/998 (0.1%)		1/996 (0.1%)
Atrial flutter	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Cardiac arrest	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Cardiac failure congestive	0/1002 (0%)		1/998 (0.1%)		1/996 (0.1%)
Myocardial infarction	1/1002 (0.1%)		1/998 (0.1%)		0/996 (0%)
Myocardial rupture	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Palpitations	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Pericarditis	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Prinzmetal angina	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Ventricular tachycardia	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Eye disorders
Cataract	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Entropion	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Retinal detachment	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Gastrointestinal disorders
Colitis	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Enteritis	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Gastric ulcer haemorrhage	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Gastrointestinal haemorrhage	0/1002 (0%)		0/998 (0%)		2/996 (0.2%)
Large intestine polyp	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Obstructive pancreatitis	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
General disorders
Chest pain	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Non-cardiac chest pain	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Sensation of foreign body	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Hepatobiliary disorders
Cholecystitis	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Cholecystitis acute	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Cholelithiasis	1/1002 (0.1%)		1/998 (0.1%)		1/996 (0.1%)
Immune system disorders
Hypersensitivity	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Infections and infestations
Appendicitis	1/1002 (0.1%)		1/998 (0.1%)		1/996 (0.1%)
Cellulitis	0/1002 (0%)		2/998 (0.2%)		0/996 (0%)
Diverticulitis	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Endocarditis	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Escherichia pyelonephritis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Extradural abscess	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Influenza	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Intervertebral discitis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Localised infection	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Osteomyelitis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Pelvic abscess	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Periorbital cellulitis	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Pneumonia	1/1002 (0.1%)		2/998 (0.2%)		1/996 (0.1%)
Pneumonia mycoplasmal	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Sepsis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Testicular abscess	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Wound infection	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Injury, poisoning and procedural complications
Adjacent segment degeneration	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Ankle fracture	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Fall	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Forearm fracture	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Hip fracture	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Joint dislocation	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Limb crushing injury	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Meniscus injury	1/1002 (0.1%)		3/998 (0.3%)		1/996 (0.1%)
Road traffic accident	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Skin abrasion	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Skin laceration	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Ulna fracture	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/1002 (0.4%)		9/998 (0.9%)		0/996 (0%)
Arthritis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Back pain	0/1002 (0%)		1/998 (0.1%)		1/996 (0.1%)
Intervertebral disc protrusion	0/1002 (0%)		2/998 (0.2%)		1/996 (0.1%)
Lumbar spinal stenosis	1/1002 (0.1%)		1/998 (0.1%)		1/996 (0.1%)
Musculoskeletal pain	0/1002 (0%)		1/998 (0.1%)		1/996 (0.1%)
Osteoarthritis	9/1002 (0.9%)		17/998 (1.7%)		4/996 (0.4%)
Osteonecrosis	0/1002 (0%)		2/998 (0.2%)		0/996 (0%)
Pain in extremity	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Rapidly progressive osteoarthritis	3/1002 (0.3%)		11/998 (1.1%)		0/996 (0%)
Rotator cuff syndrome	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Spinal osteoarthritis	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Spondylolisthesis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Subchondral insufficiency fracture	1/1002 (0.1%)		4/998 (0.4%)		2/996 (0.2%)
Thoracic spinal stenosis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/1002 (0%)		1/998 (0.1%)		1/996 (0.1%)
Cervix neoplasm	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Gastric cancer	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Invasive ductal breast carcinoma	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Lung adenocarcinoma	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Malignant melanoma	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Prostate cancer	1/1002 (0.1%)		1/998 (0.1%)		0/996 (0%)
Rectal cancer	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Thyroid adenoma	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Thyroid neoplasm	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Nervous system disorders
Brain stem infarction	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Carpal tunnel syndrome	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Cerebrovascular accident	2/1002 (0.2%)		0/998 (0%)		0/996 (0%)
Dizziness	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Loss of consciousness	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Presyncope	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Subarachnoid haemorrhage	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Syncope	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Transient ischaemic attack	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Psychiatric disorders
Major depression	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Mental status changes	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Renal and urinary disorders
Acute kidney injury	0/1002 (0%)		2/998 (0.2%)		0/996 (0%)
Ureterolithiasis	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Reproductive system and breast disorders
Cervical cyst	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Cystocele	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Ovarian cyst	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Uterine prolapse	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Chronic obstructive pulmonary disease	1/1002 (0.1%)		1/998 (0.1%)		1/996 (0.1%)
Cough	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Pleural effusion	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Pulmonary embolism	1/1002 (0.1%)		1/998 (0.1%)		0/996 (0%)
Respiratory failure	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Skin and subcutaneous tissue disorders
Rosacea	0/1002 (0%)		0/998 (0%)		1/996 (0.1%)
Vascular disorders
Deep vein thrombosis	1/1002 (0.1%)		0/998 (0%)		0/996 (0%)
Haematoma	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Hypertensive crisis	1/1002 (0.1%)		0/998 (0%)		1/996 (0.1%)
Phlebitis	0/1002 (0%)		1/998 (0.1%)		0/996 (0%)
Other (Not Including Serious) Adverse Events
	Tanezumab 2.5 mg		Tanezumab 5 mg		NSAID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	301/1002 (30%)		318/998 (31.9%)		264/996 (26.5%)
Infections and infestations
Nasopharyngitis	57/1002 (5.7%)		67/998 (6.7%)		40/996 (4%)
Upper respiratory tract infection	57/1002 (5.7%)		45/998 (4.5%)		59/996 (5.9%)
Injury, poisoning and procedural complications
Fall	65/1002 (6.5%)		52/998 (5.2%)		46/996 (4.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	131/1002 (13.1%)		160/998 (16%)		117/996 (11.7%)
Back pain	34/1002 (3.4%)		55/998 (5.5%)		34/996 (3.4%)
Nervous system disorders
Headache	56/1002 (5.6%)		45/998 (4.5%)		25/996 (2.5%)

Limitations/Caveats

2 deaths occurred after end of study and are captured in All- cause mortality section.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.