Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study In Subjects With Osteoarthritic Pain Of The Knee

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00689273
• Collaborator: (none)
• Enrollment: 159
• Locations: 22
• Arms: 2
• Actual Duration (Months): 3.7
• Patients Per Site: 7.2
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

To evaluate the efficacy, safety, tolerability, pharmacodynamics, and pharmacokinetics in patients with osteoarthritic pain of the knee. The most painful knee joint will be identified as the index joint at screening, and this joint will be used for all pain assessments throughout the study.

Condition or Disease	Intervention/Treatment	Phase
Osteoarthritis, Knee	Drug: PF-04136309; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 159 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 2-WEEK, RANDOMIZED, DOUBLE BLIND, PLACEBO CONTROLLED, PARALLEL-GROUP, PHASE 2, MULTICENTER STUDY OF PF-04136309 IN SUBJECTS WITH OSTEOARTHRITIC PAIN OF THE KNEE
• Actual Study Start Date: Aug 5, 2008
• Actual Primary Completion Date: Nov 27, 2008
• Actual Study Completion Date: Nov 27, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: PF-04136309	Drug: PF-04136309; 125 mg capsules. Dose will be 4 capsules BID for 2 weeks for a total of 500 mg for each dosing interval.
Placebo Comparator: Placebo	Drug: Placebo; Placebo will be matched to PF-04136309. Dose, frequency, and duration same as PF-04136309.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2 [Baseline, Week 2]

   WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with osteoarthritis (OA) of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.

Secondary Outcome Measures

1. Change From Baseline in WOMAC Pain Domain Score at Week 1 [Baseline, Week 1]

   WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.

2. Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2 [Baseline, Weeks 1, 2]

   WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC stiffness domain consist of 2 questions scored on 5 point Likert scale (0=minimum stiffness to 4= maximum stiffness), higher score indicates higher stiffness. It assesses stiffness (sensation of decreased ease) due to OA in study joint in past 48 hours. Total possible stiffness domain score calculated by addition of scores of each 2 questions ranged from: 0 (minimum) to 8 (maximum), higher scores indicate higher stiffness.

3. Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2 [Baseline, Weeks 1, 2]

   WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC physical function consists of 17 questions scored on 5 point Likert scale (0=minimum physical impairment to 4=maximum physical impairment), higher score indicates worse function. It assesses worse function (ability to move/perform activity) due to OA in study joint in past 48 hours. Total possible score calculated by addition of scores of each 17 questions ranged from: 0 (minimum) to 68 (maximum), higher scores indicate worse function.

4. Change From Baseline in WOMAC Total Score at Week 1 and Week 2 [Baseline, Weeks 1, 2]

   WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of the hip and/or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale (0= none to 4=extreme), higher score indicates worse function. Total WOMAC Score: summation of 24 component item scores, without any correction for relative importance of different subscales. Total score range 0 (minimum) to 96 (maximum), higher score indicate higher symptoms.

5. Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2 [Baseline, Weeks 1, 2]

   WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of hip or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale; score range: 0 (none) to 4 (extreme) where higher score indicates worse function. Importance-weighted total WOMAC score weighs 3 subscales of pain, stiffness, physical function using factors of 0.42, 0.21, and 0.37 to account for relative importance. Total score calculated by applying factors and summing all domains ranged from 0 (minimum) to 35.24 (maximum), higher score indicate higher symptoms.

6. Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average) [Baseline, Weeks 1, 2]

   NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.

7. Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14 [Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14]

   NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.

8. Number of Participants With at Least a 30 Percent (%) and 50% Reduction in Average Weekly Pain Score at Week 2: Last Observation Carried Forward (LOCF) [Baseline, Week 2]

   Participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. In this outcome measure number of participants with at least 30% and 50% reduction in average weekly pain score at Week 2 from Baseline are reported. Average weekly score at Week 2 was average of daily pain scores from Day 8 to Day 14 and at Baseline it was average of daily pain scores from Day -6 to Day 0.

9. Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2 [Baseline, Weeks 1, 2]

   Participants answered the following question: "Considering all the ways your arthritis affects you, how are you doing today?" Participants rated their condition using the scale assessing the symptoms and limitations to carry out normal daily activities. Score ranged from 1 to 5; where 1= very good (No symptoms and limitations); 2= good (mild symptoms and no limitations); 3= fair (moderate symptoms and some limitations); 4= poor (severe symptoms and inability to carry out most activities); and 5= very Poor (very severe, intolerable symptoms and inability to carry out all activities). Higher scores indicated more limitations in carrying out normal activities.

Other Outcome Measures

1. Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. SAE was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment emergent AEs included both SAEs and all non-SAEs.

2. Number of Participants With Treatment Emergent Treatment Related AEs and SAEs [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Treatment emergent AEs included both SAEs and all non-SAEs. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Relatedness to study drug was assessed by the investigator.

3. Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug.

4. Number of Treatment-Emergent AEs by Severity [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

5. Number of Treatment-Emergent Treatment-Related AEs by Severity [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

6. Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity [From Baseline up to 30 days after last dose of study drug (up to Day 44)]

   Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.

7. Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate [From Baseline up to Week 2]

   Criteria for clinical significance: sitting, standing or supine pulse rate <40 beats per minute (bpm) or >120 bpm; sitting, standing or supine diastolic blood pressure < 50 millimeter of mercury (mmHg); sitting, standing or supine systolic blood pressure < 90 mmHg. Clinical significance was judged by the investigator.

8. Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters [Baseline up to Week 2]

   Change (increase) from baseline of greater than or equal to (>=) 25% in maximum PR Interval and maximum QRS complex in milliseconds (msec). Change (increase) from baseline of >= 30 msec and less than (<) 60 msec or change >= 60 msec in maximum QTc and maximum QT interval with Fridericia's Correction (QTcF).

9. Plasma Concentration Versus Time of PF-04136309 [Day 1 and Day 14: Pre-dose and 6,7 hours post-dose]

   In this outcome measure data for reporting arm PF-04136309 was collected and reported as planned.

10. Change From Baseline in Absolute Monocyte Count at Day 14 [Baseline, Day 14]

11. Change From Baseline in Percent Monocytes at Day 14 [Baseline, Day 14]

    Monocytes (percent) were derived as monocyte absolute counts per white blood cell absolute counts*100.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female of any race, between the ages of 18 and 75 years inclusive

• Female subjects must be of non-childbearing potential and have a negative pregnancy test at Screening.

• Osteoarthritis of the knee of at least 6 months duration and meeting the American College of Rheumatology Criteria. For radiographic criteria the Xray must have been taken within the last 5 years. If none is available, one should be taken and the diagnostic criteria confirmed prior to randomization.

• Willing and able to discontinue all current analgesic therapy, including OTC pain medications and topical analgesics for OA pain, for period beginning with washout phase (lasting 2 days or 5 half-lives of patient's current analgesic medication prior to Day -6) and continuing for the entire duration of study. As an exception, acetaminophen may be used for non-joint related pain at doses ≤1 g/day at the discretion of a qualified member of the study team.

• If a subject has evidence or a history of clinically significant endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, renal, psychiatric, or neurological disease, the investigator must confirm that the disease is stable (at least 4 weeks) and under control.

• QTc interval ≤450 msec and a PR interval ≤210 msec on Screening ECG.

Exclusion Criteria:

• Pregnant or lactating females, and females of childbearing potential.

• Arthroscopy performed on index knee within 1 year of screening.

• Active depression as defined by or meeting The Hospital Anxiety and Depression Scale (HADS) of >10.

• Unwillingness to refrain from consumption of grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until completion of the study.

• First degree or higher AV block, defined as PR interval >210 msecs, bundle branch block, fascicular block or intraventricular conduction delay or clinically relevant abnormality on screening ECG.

• Active malignancy of any type or history of a malignancy within 10 years (with the exception of subjects with a history of treated basal cell carcinoma).

• Symptomatic OA of the hip ipsilateral to index knee which the patient considers more painful than the knee.

• Use of prohibited medications as listed below, in the absence of appropriate washout period. The following analgesic agents must be discontinued within 48 hours or 5 half lives of the analgesic being washed out prior to the baseline period (Day -6 to Day 0);

• NSAIDs and selective COX-2 inhibitors;

• Acetaminophen ( as an exception acetaminophen may be used for non-joint related pain at doses ≤1g/day);

• Opioids.

• Oral or I/M corticosteroids within 4 weeks prior to screening. I/A steroids within 12 weeks prior to baseline in study joint or any other joints within 4 weeks prior to baseline, or I/A hyaluronic acid within 24 weeks prior to baseline;

• Use of concomitant medications that are CYP3A inhibitors or CYP3A inducers, or that are P-glycoprotein substrates within 48 hours or 5 half lives prior to baseline.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Clinical Research-DeLand, LLC	DeLand	Florida	United States	32720
2	Arthritis & Rheumatic Care Center	South Miami	Florida	United States	33143
3	Miami Research Associates	South Miami	Florida	United States	33143
4	Diagnostic Imaging Centers	Overland Park	Kansas	United States	66212
5	Vince and Associates Clinical Research	Overland Park	Kansas	United States	66212
6	Commonwealth Biomedical Research, LLC	Madisonville	Kentucky	United States	42431
7	Covenant Health and Wellness Center	Chesterfield	Missouri	United States	63005
8	Metro Imaging West County	Creve Coeur	Missouri	United States	63141
9	Metro Imaging St. Peters	Saint Peters	Missouri	United States	63376
10	Analgesic Development Limited	New York	New York	United States	10022-1009
11	New Horizons Clinical Research	Cincinnati	Ohio	United States	45242
12	Omega Medical Research	Warwick	Rhode Island	United States	02886
13	Statcare	Warwick	Rhode Island	United States	02886
14	Diagnostics Research Group	San Antonio	Texas	United States	78229
15	South Texas Radiology Group	San Antonio	Texas	United States	78229
16	Commonwealth Orthopaedics and Rehabilitation PC	Arlington	Virginia	United States	22205
17	IntegraTrials, LLC	Arlington	Virginia	United States	22205
18	United Hospital Center Clinical Trials Office	Clarksburg	West Virginia	United States	26301
19	Seoul National University Hospital	Seoul		Korea, Republic of	110-744
20	Severance Hospital, Yonsei University College of Medicine	Seoul		Korea, Republic of	120-752
21	Samsung Medical Center	Seoul		Korea, Republic of	135-710
22	Asan Medical Center	Seoul		Korea, Republic of	138-736

Sponsors and Collaborators

• Pfizer

Investigators

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

Study Documents (Full-Text)

None provided.

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: NCT00689273
• Other Study ID Numbers: A9421006
• First Posted: Jun 3, 2008
• Last Update Posted: Jul 13, 2021
• Last Verified: Jun 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Pfizer: PF-04136309 CCR2 osteoarthritic pain knee; phase 2 placebo multicenter double-blind placebo-controlled
• Additional relevant MeSH terms: Osteoarthritis, Knee

Study Results

Participant Flow

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Period Title: Overall Study
STARTED	79	78
Treated	78	78
COMPLETED	66	73
NOT COMPLETED	13	5

Baseline Characteristics

Arm/Group Title	PF-04136309	Placebo	Total
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.	Total of all reporting groups
Overall Participants	78	78	156
Age, Customized (Count of Participants)
Less than 18 years	0 0%	0 0%	0 0%
18 to 44 years	3 3.8%	1 1.3%	4 2.6%
45 to 64 years	49 62.8%	60 76.9%	109 69.9%
Greater than or equal to 65 years	26 33.3%	17 21.8%	43 27.6%
Sex: Female, Male (Count of Participants)
Female	56 71.8%	55 70.5%	111 71.2%
Male	22 28.2%	23 29.5%	45 28.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	37 47.4%	37 47.4%	74 47.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 9%	7 9%	14 9%
White	33 42.3%	31 39.7%	64 41%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.3%	3 3.8%	4 2.6%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Domain Score at Week 2
Description	WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with osteoarthritis (OA) of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	69	74
Least Squares Mean (Standard Error) [Units on a scale]	-3.64 (0.41)	-3.15 (0.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect. One-sided alpha of 0.1 was used for the analysis.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.39
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square (LS) Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 80%; -1.23 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.57
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline in WOMAC Pain Domain Score at Week 1
Description	WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC pain domain consists of 5 questions scored on 5 point Likert scale (0=minimum pain to 4=maximum pain) where higher score indicates higher pain. It assesses amount of pain experienced due to OA in the study joint in past 48 hours. Total possible pain domain score calculated by addition of scores of each 5 questions ranged from: 0 (minimum) - 20 (maximum), higher scores indicate higher pain.
Time Frame	Baseline, Week 1

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	76	76
Least Squares Mean (Standard Error) [Units on a scale]	-2.74 (0.37)	-2.49 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 80%; -0.92 to 0.42
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.52
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in WOMAC Stiffness Domain Score at Week 1 and Week 2
Description	WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC stiffness domain consist of 2 questions scored on 5 point Likert scale (0=minimum stiffness to 4= maximum stiffness), higher score indicates higher stiffness. It assesses stiffness (sensation of decreased ease) due to OA in study joint in past 48 hours. Total possible stiffness domain score calculated by addition of scores of each 2 questions ranged from: 0 (minimum) to 8 (maximum), higher scores indicate higher stiffness.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-0.95 (0.19)	-0.78 (0.19)
Week 2	-1.39 (0.20)	-1.24 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.54
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 80%; -0.51 to 0.18
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.27
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.60
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 80%; -0.51 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in WOMAC Physical Function Domain Score at Week 1 and Week 2
Description	WOMAC: self-administered, disease-specific 24 item questionnaire which assesses clinically important, participant-relevant symptoms for pain, stiffness, and physical function in participants with OA of the hip and/or knee. It consists of 3 domains: pain, stiffness and physical function. WOMAC physical function consists of 17 questions scored on 5 point Likert scale (0=minimum physical impairment to 4=maximum physical impairment), higher score indicates worse function. It assesses worse function (ability to move/perform activity) due to OA in study joint in past 48 hours. Total possible score calculated by addition of scores of each 17 questions ranged from: 0 (minimum) to 68 (maximum), higher scores indicate worse function.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-8.63 (1.26)	-7.25 (1.29)
Week 2	-11.32 (1.41)	-8.90 (1.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.44
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.38
	Confidence Interval	(2-Sided) 80%; -3.69 to 0.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.80
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.42
	Confidence Interval	(2-Sided) 80%; -5.00 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.00
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in WOMAC Total Score at Week 1 and Week 2
Description	WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of the hip and/or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale (0= none to 4=extreme), higher score indicates worse function. Total WOMAC Score: summation of 24 component item scores, without any correction for relative importance of different subscales. Total score range 0 (minimum) to 96 (maximum), higher score indicate higher symptoms.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-12.31 (1.72)	-10.54 (1.76)
Week 2	-16.24 (1.96)	-13.22 (1.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.76
	Confidence Interval	(2-Sided) 80%; -4.94 to 1.41
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.46
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.02
	Confidence Interval	(2-Sided) 80%; -6.61 to 0.57
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.79
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in WOMAC Importance Weighted Total Score at Week 1 and Week 2
Description	WOMAC: self-administered, disease-specific instrument assessing clinically important, participant-relevant symptoms for pain, stiffness, physical function in participants with OA of hip or knee. Index consists of 24 questions: 5 (pain), 2 (stiffness), 17 (physical function). Each question was assessed on a 5-point Likert scale; score range: 0 (none) to 4 (extreme) where higher score indicates worse function. Importance-weighted total WOMAC score weighs 3 subscales of pain, stiffness, physical function using factors of 0.42, 0.21, and 0.37 to account for relative importance. Total score calculated by applying factors and summing all domains ranged from 0 (minimum) to 35.24 (maximum), higher score indicate higher symptoms.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-4.54 (0.63)	-3.90 (0.65)
Week 2	-5.97 (0.72)	-4.84 (0.73)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 80%; -1.81 to 0.52
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.91
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.12
	Confidence Interval	(2-Sided) 80%; -2.45 to 0.20
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.03
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in 11 Point Numeric Pain Rating Scale (NRS) at Week 1 and Week 2 (Weekly Average)
Description	NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-0.83 (0.14)	-0.62 (0.14)
Week 2	-1.56 (0.20)	-1.14 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.28
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.21
	Confidence Interval	(2-Sided) 80%; -0.46 to 0.04
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.19
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 80%; -0.78 to -0.06
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in 11 Point NRS at Each Day From Day 1 to Day 14
Description	NRS: participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain.
Time Frame	Baseline, Days 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Day 1	-0.26 (0.20)	-0.09 (0.19)
Day 2	-0.67 (0.20)	-0.22 (0.20)
Day 3	-0.81 (0.20)	-0.46 (0.20)
Day 4	-0.91 (0.20)	-0.58 (0.20)
Day 5	-1.02 (0.20)	-0.80 (0.20)
Day 6	-1.11 (0.20)	-0.97 (0.20)
Day 7	-1.23 (0.20)	-1.04 (0.19)
Day 8	-1.50 (0.20)	-1.04 (0.20)
Day 9	-1.35 (0.20)	-1.03 (0.20)
Day 10	-1.49 (0.20)	-0.84 (0.20)
Day 11	-1.60 (0.20)	-1.03 (0.20)
Day 12	-1.82 (0.20)	-1.23 (0.20)
Day 13	-1.76 (0.20)	-1.43 (0.20)
Day 14	-1.82 (0.20)	-1.36 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 1: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 80%; -0.52 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 2: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 80%; -0.81 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 3: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.20
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.35
	Confidence Interval	(2-Sided) 80%; -0.71 to 0.00
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 4: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.23
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 80%; -0.69 to 0.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 5: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.41
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 80%; -0.58 to 0.13
	Parameter Dispersion	Type: Standard Deviation; Value: 0.28
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 6: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.62
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 80%; -0.49 to 0.22
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 7: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.49
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.19
	Confidence Interval	(2-Sided) 80%; -0.55 to 0.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 8: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.46
	Confidence Interval	(2-Sided) 80%; -0.81 to -0.10
	Parameter Dispersion	Type: Standard Deviation; Value: 0.28
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 9: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 80%; -0.69 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 10: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.65
	Confidence Interval	(2-Sided) 80%; -1.01 to -0.28
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 11: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.57
	Confidence Interval	(2-Sided) 80%; -0.93 to -0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 12: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.59
	Confidence Interval	(2-Sided) 80%; -0.95 to -0.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 13: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.33
	Confidence Interval	(2-Sided) 80%; -0.70 to 0.03
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Day 14: Results were obtained from a mixed effect repeated measure model using compound symmetry covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.11
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	-0.45
	Confidence Interval	(2-Sided) 80%; -0.82 to -0.09
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.28
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With at Least a 30 Percent (%) and 50% Reduction in Average Weekly Pain Score at Week 2: Last Observation Carried Forward (LOCF)
Description	Participant rated their daily pain on 11-point Likert scale ranging from 0 (no pain) to 10 (worst possible pain) during past 24-hour period. Higher score indicates greater level of pain. In this outcome measure number of participants with at least 30% and 50% reduction in average weekly pain score at Week 2 from Baseline are reported. Average weekly score at Week 2 was average of daily pain scores from Day 8 to Day 14 and at Baseline it was average of daily pain scores from Day -6 to Day 0.
Time Frame	Baseline, Week 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. LOCF method was used to impute missing values.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
30% Reduction	27 34.6%	20 25.6%
50% Reduction	14 17.9%	10 12.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	30% Reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.22
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	50% Reduction
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

10. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Arthritic Condition at Week 1 and Week 2
Description	Participants answered the following question: "Considering all the ways your arthritis affects you, how are you doing today?" Participants rated their condition using the scale assessing the symptoms and limitations to carry out normal daily activities. Score ranged from 1 to 5; where 1= very good (No symptoms and limitations); 2= good (mild symptoms and no limitations); 3= fair (moderate symptoms and some limitations); 4= poor (severe symptoms and inability to carry out most activities); and 5= very Poor (very severe, intolerable symptoms and inability to carry out all activities). Higher scores indicated more limitations in carrying out normal activities.
Time Frame	Baseline, Weeks 1, 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Week 1	-0.42 (0.09)	-0.32 (0.09)
Week 2	-0.56 (0.09)	-0.44 (0.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 1: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 80%; -0.27 to 0.07
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	PF-04136309, Placebo
	Comments	Week 2: Results were obtained from a mixed effect repeated measure model using unstructured covariance matrix. The model included random-effect terms for participant, and fixed-effect terms for baseline response, treatment group, time, treatment-by-time interaction, and country effect.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 80%; -0.29 to 0.05
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.13
	Estimation Comments

11. Other Pre-specified 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 with the study treatment. SAE was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. Treatment emergent AEs included both SAEs and all non-SAEs.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Treatment Emergent AEs	22 28.2%	21 26.9%
Treatment Emergent SAEs	0 0%	0 0%

12. Other Pre-specified Outcome

Title	Number of Participants With Treatment Emergent Treatment Related AEs and SAEs
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Treatment emergent AEs included both SAEs and all non-SAEs. A treatment-related SAE was a treatment-related AE and was defined as any untoward medical occurrence at any dose that: was fatal or life-threatening; resulted in persistent or significant disability/incapacity; constituted a congenital anomaly/birth defect; was medically significant; required inpatient hospitalization or prolongation of existing hospitalization. Relatedness to study drug was assessed by the investigator.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Treatment Emergent Treatment Related AEs	13 16.7%	16 20.5%
Treatment Emergent Treatment Related SAEs	0 0%	0 0%

13. Other Pre-specified Outcome

Title	Number of Participants Who Discontinued Due to Treatment Emergent AEs and Treatment Emergent Treatment Related AEs
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Treatment Emergent AEs	3 3.8%	1 1.3%
Treatment Emergent Treatment Related AEs	1 1.3%	1 1.3%

14. Other Pre-specified Outcome

Title	Number of Treatment-Emergent AEs by Severity
Description	Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Mild	24	29
Moderate	2	9
Severe	2	1

15. Other Pre-specified Outcome

Title	Number of Treatment-Emergent Treatment-Related AEs by Severity
Description	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship with the study treatment. Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Mild	13	18
Moderate	1	4
Severe	1	1

16. Other Pre-specified Outcome

Title	Number of Participants Who Discontinued Due to Treatment-Emergent AEs According to Severity
Description	Treatment-emergent AEs were events that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. The severity grades (mild, moderate and severe) were defined as - Mild: did not interfere with participant's usual function, Moderate: Interfered to some extent with participant's usual function and Severe: Interfered significantly with participant's usual function.
Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Mild	1 1.3%	1 1.3%
Moderate	1 1.3%	0 0%
Severe	1 1.3%	0 0%

17. Other Pre-specified Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Blood Pressure and Pulse Rate
Description	Criteria for clinical significance: sitting, standing or supine pulse rate <40 beats per minute (bpm) or >120 bpm; sitting, standing or supine diastolic blood pressure < 50 millimeter of mercury (mmHg); sitting, standing or supine systolic blood pressure < 90 mmHg. Clinical significance was judged by the investigator.
Time Frame	From Baseline up to Week 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78	78
Count of Participants [Participants]	0 0%	0 0%

18. Other Pre-specified Outcome

Title	Number of Participants With Change (Increase) From Baseline in Electrocardiogram (ECG) Parameters
Description	Change (increase) from baseline of greater than or equal to (>=) 25% in maximum PR Interval and maximum QRS complex in milliseconds (msec). Change (increase) from baseline of >= 30 msec and less than (<) 60 msec or change >= 60 msec in maximum QTc and maximum QT interval with Fridericia's Correction (QTcF).
Time Frame	Baseline up to Week 2

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified rows.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	77	77
Maximum PR Interval increase from baseline; change >=25%	0 0%	0 0%
Maximum QRS Complex increase from baseline; change >=25%	0 0%	0 0%
Maximum QTc Interval increase from baseline; Change >=30 msec and < 60 msec	1 1.3%	0 0%
Maximum QTc Interval increase from baseline; Change >=60 msec	1 1.3%	0 0%
Maximum QTcF Interval increase from baseline; Change >=30 msec and < 60 msec	1 1.3%	0 0%
Maximum QTcF Interval increase from baseline; Change >=60 msec	1 1.3%	0 0%

19. Other Pre-specified Outcome

Title	Plasma Concentration Versus Time of PF-04136309
Description	In this outcome measure data for reporting arm PF-04136309 was collected and reported as planned.
Time Frame	Day 1 and Day 14: Pre-dose and 6,7 hours post-dose

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here, 'number analyzed' signifies participants evaluable for this outcome measure for specified time points.

Arm/Group Title	PF-04136309
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	78
Day 1: pre-dose	257.90 (276.38)
Day 1: 6 hours post-dose	587.54 (626.53)
Day 1: 7 hours post-dose	590.85 (615.06)
Day 14: 0 hours pre-dose	227.42 (259.21)
Day 14: 6 hours post-dose	388.00 (244.98)
Day 14: 7 hours post-dose	426.14 (266.11)

20. Other Pre-specified Outcome

Title	Change From Baseline in Absolute Monocyte Count at Day 14
Time Frame	Baseline, Day 14

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	77	77
Median (Inter-Quartile Range) [Thousand cells per millimeter cube]	-0.13	-0.01

21. Other Pre-specified Outcome

Title	Change From Baseline in Percent Monocytes at Day 14
Description	Monocytes (percent) were derived as monocyte absolute counts per white blood cell absolute counts*100.
Time Frame	Baseline, Day 14

Outcome Measure Data

Analysis Population Description

FAS included all randomized participants who took at least 1 dose of study drug. Here 'Overall number of participants analyzed' signifies participants evaluable for this outcome measure.

Arm/Group Title	PF-04136309	Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.	Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
Measure Participants	77	77
Median (Inter-Quartile Range) [Percent monocytes]	-1.7	0.0

Adverse Events

Time Frame	From Baseline up to 30 days after last dose of study drug (up to Day 44)
Adverse Event Reporting Description	The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. FAS included all randomized participants who received at least 1 dose of study drug.
Arm/Group Title	PF-04136309		Placebo
Arm/Group Description	Participants with osteoarthritis of knee received four 125 milligram (mg) capsules of PF-04136309, orally twice daily for 13 days and single morning dose on Day 14.		Participants with osteoarthritis of knee received placebo matched to four PF-04136309 125 mg capsules, orally twice daily for 13 days and single morning dose on Day 14.
All Cause Mortality
	PF-04136309		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/78 (0%)		0/78 (0%)
Serious Adverse Events
	PF-04136309		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/78 (0%)		0/78 (0%)
Other (Not Including Serious) Adverse Events
	PF-04136309		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	22/78 (28.2%)		21/78 (26.9%)
Cardiac disorders
Atrial fibrillation	1/78 (1.3%)		1/78 (1.3%)
Sinus tachycardia	1/78 (1.3%)		0/78 (0%)
Eye disorders
Eye pain	0/78 (0%)		1/78 (1.3%)
Vision blurred	0/78 (0%)		1/78 (1.3%)
Gastrointestinal disorders
Abdominal pain	1/78 (1.3%)		0/78 (0%)
Constipation	2/78 (2.6%)		0/78 (0%)
Diarrhoea	0/78 (0%)		4/78 (5.1%)
Dry mouth	1/78 (1.3%)		0/78 (0%)
Dyspepsia	0/78 (0%)		1/78 (1.3%)
Nausea	2/78 (2.6%)		3/78 (3.8%)
General disorders
Chest pain	1/78 (1.3%)		0/78 (0%)
Fatigue	0/78 (0%)		2/78 (2.6%)
Oedema peripheral	0/78 (0%)		2/78 (2.6%)
Pain	1/78 (1.3%)		1/78 (1.3%)
Ulcer	1/78 (1.3%)		0/78 (0%)
Infections and infestations
Influenza	0/78 (0%)		1/78 (1.3%)
Upper respiratory tract infection	1/78 (1.3%)		1/78 (1.3%)
Urinary tract infection	0/78 (0%)		1/78 (1.3%)
Injury, poisoning and procedural complications
Contusion	0/78 (0%)		1/78 (1.3%)
Fall	0/78 (0%)		1/78 (1.3%)
Joint injury	1/78 (1.3%)		0/78 (0%)
Periorbital haematoma	0/78 (0%)		1/78 (1.3%)
Investigations
Blood creatinine increased	0/78 (0%)		2/78 (2.6%)
Blood glucose increased	0/78 (0%)		1/78 (1.3%)
Creatinine renal clearance decreased	0/78 (0%)		1/78 (1.3%)
Electrocardiogram QT prolonged	0/78 (0%)		1/78 (1.3%)
Electrocardiogram T wave amplitude decreased	0/78 (0%)		1/78 (1.3%)
Hepatic enzyme increased	1/78 (1.3%)		0/78 (0%)
Metabolism and nutrition disorders
Hypercalcaemia	1/78 (1.3%)		0/78 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/78 (0%)		2/78 (2.6%)
Muscle spasms	2/78 (2.6%)		0/78 (0%)
Musculoskeletal pain	0/78 (0%)		1/78 (1.3%)
Myalgia	1/78 (1.3%)		0/78 (0%)
Nervous system disorders
Dizziness	2/78 (2.6%)		0/78 (0%)
Headache	6/78 (7.7%)		3/78 (3.8%)
Somnolence	0/78 (0%)		2/78 (2.6%)
Skin and subcutaneous tissue disorders
Acne	2/78 (2.6%)		0/78 (0%)
Pruritus	0/78 (0%)		1/78 (1.3%)
Vascular disorders
Flushing	0/78 (0%)		1/78 (1.3%)
Hypertension	0/78 (0%)		1/78 (1.3%)

Limitations/Caveats

[Not Specified]

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.