Phase I Study Of The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of PF-04236921 In Patients With Rheumatoid Arthritis

• Sponsor: Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00838565
• Collaborator: (none)
• Enrollment: 41
• Locations: 8
• Arms: 2
• Actual Duration (Months): 32.5
• Patients Per Site: 5.1
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study will evaluate the safety and tolerability of PF-04236921 administered monthly as three intravenous infusions. Each group of patients will be assigned to a dose level; Safety and tolerability of a low dose level will be required before proceeding to successively higher dose levels. Blood tests will be performed to measure the amount of drug and changes in measures of inflammation.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Placebo; Drug: dose level 1; Drug: dose level 2; Drug: dose level 3; Drug: dose level 4	Phase 1

Detailed Description

Safety and Tolerability and Pharmacokinetic/Pharmacodynamic assessment of inflammation-related biomarkers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Phase 1, Randomized, Patient And Investigator-blind, Placebo-controlled Study To Investigate The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Multiple Intravenously Administered Doses Of Pf-04236921 In Patients With Rheumatoid Arthritis Receiving Methotrexate
• Actual Study Start Date: May 20, 2009
• Actual Primary Completion Date: Feb 2, 2012
• Actual Study Completion Date: Feb 2, 2012

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; intravenous infusion on three consecutive months
Experimental: PF-04236921	Drug: dose level 1; intravenous infusion on three consecutive months; Drug: dose level 2; intravenous infusion on three consecutive months; Drug: dose level 3; intravenous infusion on three consecutive months; Drug: dose level 4; intravenous infusion on 3 consecutive months

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)]

   An AE was any untoward medical occurrence in a participant who received study medication without regard to possibility of causal relationship. An 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 are events between first dose of study medication and up to 28 days after last dose or until serum PF-04236921 concentrations were below the LLOQ that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

2. Number of Participants With Positive Anti-drug Antibodies Response [Day 1, 28, 56, 84, 174, 354, End of Study (Day 624)]

3. Maximum Observed Serum Concentration (Cmax): Day 1 [Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose]

4. Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1 [Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose]

5. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1 [Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose]

   AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).

6. Maximum Observed Serum Concentration (Cmax): Day 28 [Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose]

7. Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28 [Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose]

8. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28 [Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose]

   AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).

9. Maximum Observed Serum Concentration (Cmax): Day 56 [Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose]

10. Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56 [Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose]

11. Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56 [Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose]

    AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).

12. Serum Decay Half-Life (t1/2): Day 56 [Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose]

    Serum decay half-life is the time measured for the serum concentration to decrease by one half.

Other Outcome Measures

1. Change From Baseline in C-Reactive Protein (CRP) Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation [Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation]

   The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra sensitive assay. A decrease in the level of CRP indicates reduction in inflammation.

2. Change From Baseline in Log CRP Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 [Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624]

   The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

3. Change From Baseline in Absolute Neutrophil Counts at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation [Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation]

4. Change From Baseline in Free Interleukin-6 (IL-6) Concentrations at Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579 and 624 [Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624]

   Serum samples were analyzed for IL-6 concentrations using a validated analytical colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) method.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Rheumatoid Arthritis on a stable dose of methotrexate

• Rheumatoid Arthritis disease activity as assessed by blood tests

Exclusion Criteria:

• Serious or uncontrolled medical conditions

• Current or recent treatment with disease-modifying drugs other than methotrexate including but not limited to leflunomide, sulfasalazine, etanercept, infliximab, adalimumab, abatacept, rituximab

• Current oral glucocorticoid dose of more than 10 mg/d prednisone equivalent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Allergy, Asthma, Arthritis, & Lung	Daytona Beach	Florida	United States	32114
2	Millennium Research	Ormond Beach	Florida	United States	32174
3	Altoona Center for Clinical Research	Duncansville	Pennsylvania	United States	16635
4	Inha University Hospital, Medicine/Rheumatology	Incheon		Korea, Republic of	400-711
5	Seoul National University Hospital, Rheumatology, Internal Medicine	Seoul		Korea, Republic of	110-744
6	Yonsei University College of Medicine, Severance Hospital, Clinical Trial Center	Seoul		Korea, Republic of	120-752
7	Hospital Clinico Universitario de Santiago	Santiago de Compostela	A Coruña	Spain	15706
8	Complexo Hospitalario Universitario A Coruña	A Coruña		Spain	15006

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: NCT00838565
• Other Study ID Numbers: B0151002; 2009-009866-15
• First Posted: Feb 6, 2009
• Last Update Posted: Nov 2, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by Pfizer: Safety and tolerability Pharmacokinetics Pharmacodynamics PF-04236921
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Period Title: Overall Study
STARTED	9	7	6	6	6	7
Treated	9	6	6	6	6	7
COMPLETED	9	4	5	6	6	5
NOT COMPLETED	0	3	1	0	0	2

Baseline Characteristics

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg	Total
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	Total of all reporting groups
Overall Participants	9	6	6	6	6	7	40
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.6 (8.5)	61.7 (7.9)	49.8 (13.5)	46.0 (4.1)	56.7 (8.9)	55.4 (9.8)	55.2 (10.1)
Sex: Female, Male (Count of Participants)
Female	8 88.9%	6 100%	5 83.3%	5 83.3%	4 66.7%	6 85.7%	34 85%
Male	1 11.1%	0 0%	1 16.7%	1 16.7%	2 33.3%	1 14.3%	6 15%

Outcome Measures

1. Primary 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 medication without regard to possibility of causal relationship. An 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 are events between first dose of study medication and up to 28 days after last dose or until serum PF-04236921 concentrations were below the LLOQ that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.
Time Frame	Baseline up to 28 days after last dose of study medication or until serum PF-04236921 concentrations below the LLOQ (up to Day 624)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication.

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	9	6	6	6	6	7
AEs	9 100%	4 66.7%	4 66.7%	6 100%	6 100%	5 71.4%
SAEs	0 0%	0 0%	0 0%	2 33.3%	1 16.7%	0 0%

2. Primary Outcome

Title	Number of Participants With Positive Anti-drug Antibodies Response
Time Frame	Day 1, 28, 56, 84, 174, 354, End of Study (Day 624)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of study medication. Here 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	6	6	6	7
Day 1	0 0%	0 0%	0 0%	0 0%	0 0%
Day 28	0 0%	0 0%	0 0%	0 0%	0 0%
Day 56	0 0%	0 0%	0 0%	0 0%	0 0%
Day 84	0 0%	0 0%	0 0%	0 0%	0 0%
Day 174	0 0%	0 0%	0 0%	0 0%	0 0%
Day 354	0 0%	0 0%	0 0%	0 0%
End of Study	0 0%	0 0%	0 0%	0 0%	0 0%

3. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax): Day 1
Time Frame	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	6	6	6	7
Geometric Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]	421.6 (162.89)	4631 (1429.9)	11320 (2167.2)	42290 (7883.0)	66280 (59405)

4. Primary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 1
Time Frame	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	6	6	6	7
Median (Full Range) [days]	0.0521	0.0521	0.0521	0.0521	0.0521

5. Primary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 1
Description	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame	Day 1: Pre-dose (0 hour), 15 minutes, 168 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	6	6	6	7
Geometric Mean (Standard Deviation) [ng*day/mL]	1899 (1090.1)	19570 (5335.7)	54140 (9345.0)	206000 (40578)	348500 (336540)

6. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax): Day 28
Time Frame	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Geometric Mean (Standard Deviation) [ng/mL]	617.6 (430.18)	4719 (1807.2)	13680 (3453.2)	57280 (6396.4)	158300 (50966)

7. Primary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 28
Time Frame	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Median (Full Range) [days]	0.0521	0.0521	0.0521	0.0521	0.0521

8. Primary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 28
Description	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame	Day 28: Pre-dose (0 hour), 15 minutes, 168 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Geometric Mean (Standard Deviation) [ng*day/mL]	3104 (2369.7)	21660 (7232.7)	76510 (19496)	316900 (45597)	767900 (213320)

9. Primary Outcome

Title	Maximum Observed Serum Concentration (Cmax): Day 56
Time Frame	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Geometric Mean (Standard Deviation) [ng/mL]	741.0 (977.35)	4424 (1384.8)	19650 (1537.5)	64850 (13289)	164600 (35644)

10. Primary Outcome

Title	Time to Reach Maximum Observed Serum Concentration (Tmax): Day 56
Time Frame	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Median (Full Range) [days]	0.0521	0.0521	0.0521	0.0521	0.0521

11. Primary Outcome

Title	Area Under the Curve From Time Zero to Last Quantifiable Concentration [AUC (0-168)]: Day 56
Description	AUC (0-168) = Area under the serum concentration versus time curve from time zero (pre-dose) to 168 hours (0-168).
Time Frame	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	6	5	6	6	7
Geometric Mean (Standard Deviation) [ng*day/mL]	3730 (4479.8)	23200 (7558.6)	101100 (6438.2)	389100 (71949)	912200 (209610)

12. Primary Outcome

Title	Serum Decay Half-Life (t1/2): Day 56
Description	Serum decay half-life is the time measured for the serum concentration to decrease by one half.
Time Frame	Day 56: Pre-dose (0 hour), 15 minutes, 168 hours, 336 hours, 672 hours post-dose

Outcome Measure Data

Analysis Population Description

PK parameter analysis population included all enrolled and treated participants who had at least 1 of the PK parameters of interest. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.

Arm/Group Title	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	2	5	5	6	6
Median (Full Range) [days]	45.50 (NA)	36.90 (11.010)	45.30 (9.5166)	38.80 (6.9500)	51.70 (9.2230)

13. Other Pre-specified Outcome

Title	Change From Baseline in C-Reactive Protein (CRP) Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation
Description	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultra sensitive assay. A decrease in the level of CRP indicates reduction in inflammation.
Time Frame	Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation

Outcome Measure Data

Analysis Population Description

Pharmacodynamic analysis set included all enrolled participants who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter. Data collected at Early Discontinuation included those subjects who left the study early.'N' (number of participants analyzed) = participants who were evaluable for this measure.

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	9	6	6	5	6	7
Baseline	11.54 (12.452)	9.95 (7.886)	11.01 (6.419)	7.23 (8.316)	8.88 (5.797)	17.91 (25.572)
Change at Day 7	-0.09 (7.128)	-6.36 (8.322)	-9.85 (5.830)	-6.43 (7.766)	-8.26 (5.747)	-17.31 (25.317)
Change at Day 14	-2.63 (10.877)	-5.81 (9.019)	-10.03 (6.134)	-6.69 (8.357)	-8.56 (5.827)	-17.52 (25.571)
Change at Day 28	1.06 (5.153)	-4.48 (8.635)	-9.98 (6.168)	-6.70 (8.402)	-8.59 (5.797)	-17.52 (25.634)
Change at Day 35	0.74 (6.859)	-6.51 (8.817)	-11.10 (6.617)	-6.52 (8.515)	-8.63 (5.824)	-17.56 (25.608)
Change at Day 42	-0.06 (6.823)	-6.60 (8.299)	-11.02 (6.653)	-6.82 (8.384)	-8.65 (5.833)	-17.59 (25.614)
Change at Day 56	-0.07 (6.724)	-6.14 (8.918)	-10.68 (6.503)	-6.65 (8.453)	-8.66 (5.817)	-17.59 (25.611)
Change at Day 63	-0.10 (8.214)	-7.83 (8.284)	-11.35 (6.758)	-6.67 (8.472)	-8.68 (5.812)	-17.58 (25.611)
Change at Day 70	1.68 (13.334)	-7.67 (8.263)	-11.25 (6.740)	-6.82 (8.441)	-8.69 (5.810)	-17.60 (25.608)
Change at Day 84	5.16 (26.869)	-6.23 (9.130)	-10.88 (6.555)	-6.88 (8.441)	-8.54 (5.760)	-17.58 (25.587)
Change at Day 129	5.10 (23.998)	-8.49 (10.327)	-10.26 (5.772)	-6.63 (8.513)	-8.65 (5.840)	-17.66 (25.605)
Change at Day 174	2.42 (15.773)	-4.55 (0.735)	-8.73 (4.550)	-4.28 (4.545)	-8.57 (5.781)	-17.62 (25.581)
Change at Day 219	4.35 (18.530)	4.01 (10.083)	-6.22 (4.790)	-6.40 (8.602)	-8.66 (5.807)	-19.43 (26.221)
Change at Day 264	-5.33 (6.033)	-6.30 (NA)	-4.06 (1.961)	-2.58 (1.056)	-8.07 (5.922)	-16.60 (28.318)
Change at Day 309	-6.19 (7.987)	-4.36 (1.761)	-5.80 (8.951)	-7.63 (6.599)	-16.52 (28.364)
Change at Day 354	-3.33 (12.217)	-2.30 (NA)	-5.11 (9.482)	-8.12 (5.849)	-16.61 (28.313)
Change at Day 399	-2.49 (8.119)	-6.47 (8.596)	4.68 (32.401)	-16.56 (28.330)
Change at Day 444	-15.00 (NA)	-0.79 (NA)	-4.78 (4.694)	-15.57 (28.927)
Change at Day 489	-14.38 (NA)	-1.05 (NA)	-1.80 (0.870)	-16.47 (28.357)
Change at Day 534	-6.82 (NA)	-0.86 (NA)	-2.34 (NA)	-16.25 (28.463)
Change at Day 579	-13.88 (NA)	-15.81 (28.620)
Change at Day 624	-23.45 (37.575)
Change at Early Discontinuation	2.30 (NA)

14. Other Pre-specified Outcome

Title	Change From Baseline in Log CRP Concentrations at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624
Description	The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.
Time Frame	Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624

Outcome Measure Data

Analysis Population Description

Data for this outcome measure was not assessed since this measure was analyzed as per sponsor discretion as the change from baseline in CRP in this study was well demonstrated with the raw CRP data. Therefore, log transformation of CRP was not performed.

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	0	0	0	0	0	0

15. Other Pre-specified Outcome

Title	Change From Baseline in Absolute Neutrophil Counts at Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624 and Early Discontinuation
Time Frame	Baseline, Day 7, 14, 28, 35, 42, 56, 63, 70, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624, Early Discontinuation

Outcome Measure Data

Analysis Population Description

Pharmacodynamic analysis set included all enrolled participants who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter.Data collected at Early Discontinuation included those subjects who left the study early. 'N' (number of participants analyzed) = participants who were evaluable for this measure.

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	8	5	6	6	5	7
Baseline	3.41 (1.458)	4.13 (1.161)	4.35 (1.203)	4.38 (1.791)	4.26 (1.058)	3.13 (0.950)
Change at Day 7	0.27 (0.932)	-0.16 (1.707)	-1.61 (0.936)	-0.61 (0.756)	-1.87 (0.550)	-1.08 (0.671)
Change at Day 14	0.34 (0.919)	-0.71 (1.145)	-1.34 (0.586)	-0.70 (0.899)	-1.91 (0.660)	-0.78 (0.588)
Change at Day 28	0.24 (0.632)	-0.58 (1.828)	-0.56 (1.278)	-0.66 (0.764)	-1.91 (0.460)	-0.60 (0.637)
Change at Day 35	0.34 (0.987)	-0.39 (1.394)	-1.92 (1.051)	-1.28 (0.574)	-2.08 (0.756)	-0.70 (0.859)
Change at Day 42	0.48 (0.842)	-0.67 (1.834)	-1.19 (0.763)	-0.54 (1.094)	-1.78 (0.954)	-0.83 (0.617)
Change at Day 56	0.49 (1.085)	-0.79 (1.071)	-1.75 (1.024)	-1.11 (0.682)	-1.47 (0.778)	-1.27 (0.674)
Change at Day 63	-0.45 (1.683)	-1.17 (1.742)	-1.36 (0.548)	-1.23 (0.872)	-1.69 (0.979)	-1.04 (0.657)
Change at Day 70	0.57 (0.883)	-1.18 (1.054)	-1.80 (0.952)	-0.48 (0.746)	-2.20 (1.218)	-1.11 (0.871)
Change at Day 84	-0.05 (0.427)	-0.87 (1.257)	-1.77 (1.138)	-0.33 (1.740)	-1.02 (1.858)	-1.24 (0.719)
Change at Day 129	1.56 (2.271)	-0.35 (0.289)	-1.40 (1.424)	-0.84 (1.005)	-1.62 (0.757)	-0.60 (0.458)
Change at Day 174	0.49 (1.222)	-0.51 (1.944)	-1.27 (1.468)	-0.09 (2.183)	-1.25 (1.254)	-0.58 (0.254)
Change at Day 219	0.69 (1.071)	-0.99 (0.994)	-1.11 (1.111)	-0.75 (0.876)	-1.71 (0.906)	-0.82 (0.667)
Change at Day 264	0.69 (0.653)	-1.48 (NA)	-0.87 (0.969)	-1.28 (0.857)	-1.36 (1.237)	-0.64 (0.683)
Change at Day 309	0.05 (0.452)	-2.61 (0.709)	-1.34 (0.726)	-1.01 (0.990)	-0.42 (0.726)
Change at Day 354	1.46 (0.296)	-2.02 (NA)	-0.88 (0.448)	-1.33 (0.624)	-0.16 (0.717)
Change at Day 399	0.44 (0.922)	-0.61 (0.781)	0.34 (2.056)	-0.11 (0.901)
Change at Day 444	0.47 (NA)	-0.32 (NA)	-0.96 (2.067)	0.11 (1.064)
Change at Day 489	0.68 (NA)	-1.24 (0.564)	0.05 (0.769)
Change at Day 534	-0.10 (NA)	-0.61 (NA)	-1.07 (NA)	-0.22 (0.685)
Change at Day 579	0.16 (NA)	0.41 (0.566)
Change at Day 624	0.10 (0.792)
Change at Early Discontinuation	0.00 (0.498)	0.93 (1.106)	-1.00 (0.899)	-0.69 (1.087)	-0.63 (0.849)	-0.07 (0.948)

16. Other Pre-specified Outcome

Title	Change From Baseline in Free Interleukin-6 (IL-6) Concentrations at Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579 and 624
Description	Serum samples were analyzed for IL-6 concentrations using a validated analytical colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) method.
Time Frame	Baseline, Day 28, 56, 84, 129, 174, 219, 264, 309, 354, 399, 444, 489, 534, 579, 624

Outcome Measure Data

Analysis Population Description

Pharmacodynamic analysis set included all enrolled participants who received at least 1 dose of study medication and had at least 1 pharmacodynamic parameter. n=participants evaluable for this measure at specified time points for each arm, respectively.

Arm/Group Title	Placebo	PF-04236921 1 mg	PF-04236921 10 mg	PF-04236921 30 mg	PF-04236921 100 mg	PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.	PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
Measure Participants	9	6	6	6	6	7
Baseline	12.55 (14.593)	9.11 (7.204)	17.82 (12.433)	3.96 (3.272)	11.75 (9.797)	9.49 (11.744)
Change at Day 28	0.45 (5.383)	-2.16 (5.767)	-13.12 (13.086)	-2.40 (3.272)	-9.70 (9.147)	-7.25 (10.337)
Change at Day 56	-2.00 (8.081)	-3.04 (6.583)	-16.14 (12.643)	-1.80 (3.342)	-10.19 (9.797)	-7.93 (11.744)
Change at Day 84	-0.04 (14.524)	-5.60 (7.278)	-14.96 (14.406)	-2.08 (3.623)	-10.19 (9.797)	-7.29 (11.313)
Change at Day 129	-1.25 (8.691)	-1.90 (9.291)	-13.39 (13.627)	-1.89 (3.907)	-10.19 (9.797)	-7.16 (11.507)
Change at Day 174	4.53 (20.905)	-4.70 (14.863)	-11.63 (12.903)	-1.34 (4.056)	-10.19 (9.797)	-7.22 (11.332)
Change at Day 219	4.51 (19.163)	-2.51 (16.794)	-14.23 (13.524)	-0.77 (3.830)	-10.19 (9.797)	-3.89 (7.796)
Change at Day 264	-2.33 (14.034)	-17.94 (NA)	-1.03 (17.395)	-1.39 (2.609)	-9.93 (9.856)	-1.33 (1.905)
Change at Day 309	-1.36 (2.356)	-9.19 (18.993)	-1.67 (2.506)	-8.87 (10.655)	-1.33 (1.905)
Change at Day 354	-1.36 (2.356)	-20.00 (NA)	-2.34 (3.487)	-8.61 (10.701)	-1.33 (1.905)
Change at Day 399	-1.36 (2.356)	2.15 (4.508)	-3.74 (17.157)	-1.33 (1.905)
Change at Day 444	-4.08 (NA)	4.69 (NA)	-8.19 (12.557)	-0.78 (1.865)
Change at Day 489	-4.08 (NA)	-2.51 (NA)	-6.31 (19.778)	-0.44 (2.157)
Change at Day 534	-4.08 (NA)	-2.51 (NA)	-20.93 (NA)	-1.33 (1.905)
Change at Day 579	-4.08 (NA)	-1.33 (1.905)
Change at Day 624	-0.85 (1.472)

Adverse Events

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.
Arm/Group Title	Placebo		PF-04236921 1 mg		PF-04236921 10 mg		PF-04236921 30 mg		PF-04236921 100 mg		PF-04236921 250 mg
Arm/Group Description	Placebo matched to PF-04236921 intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.		PF-04236921 1 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.		PF-04236921 10 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.		PF-04236921 30 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.		PF-04236921 100 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.		PF-04236921 250 mg intravenous infusion over approximately 1 hour on Day 1, 28 and 56. Methotrexate orally or parenterally starting from at least 16 weeks prior to randomization as per local standard-of-care practice followed by a stable dose of methotrexate between 7.5 to 25 mg per week from at least 6 weeks prior to randomization to Day 84. Participants were followed up to 624 days.
All Cause Mortality
	Placebo		PF-04236921 1 mg		PF-04236921 10 mg		PF-04236921 30 mg		PF-04236921 100 mg		PF-04236921 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		PF-04236921 1 mg		PF-04236921 10 mg		PF-04236921 30 mg		PF-04236921 100 mg		PF-04236921 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/9 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/6 (16.7%)		0/7 (0%)
General disorders
Chest pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Infections and infestations
Abscess limb	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Pneumonia	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Plantar fasciitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		PF-04236921 1 mg		PF-04236921 10 mg		PF-04236921 30 mg		PF-04236921 100 mg		PF-04236921 250 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/9 (100%)		4/6 (66.7%)		4/6 (66.7%)		6/6 (100%)		6/6 (100%)		5/7 (71.4%)
Blood and lymphatic system disorders
Anaemia	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Leukopenia	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		1/7 (14.3%)
Neutropenia	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Cardiac disorders
Atrial fibrillation	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Ear and labyrinth disorders
Tinnitus	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Eye disorders
Conjunctivitis allergic	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Eye pain	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Gastrointestinal disorders
Abdominal pain	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Abdominal pain upper	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/7 (0%)
Colonic polyp	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Constipation	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Dental caries	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Diarrhoea	2/9 (22.2%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Dry mouth	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Dyspepsia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Epigastric discomfort	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)
Gastritis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Gastrooesophageal reflux disease	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Nausea	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/7 (14.3%)
Periodontal disease	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Stomatitis	0/9 (0%)		1/6 (16.7%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)
Vomiting	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
General disorders
Asthenia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Feeling cold	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Oedema peripheral	1/9 (11.1%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Pain	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Infections and infestations
Acute tonsillitis	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Bronchitis	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Cystitis	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		2/6 (33.3%)		0/6 (0%)		0/7 (0%)
Folliculitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Gastroenteritis viral	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Nasopharyngitis	3/9 (33.3%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/6 (33.3%)		2/7 (28.6%)
Oral herpes	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Pharyngitis	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Rhinitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Sinusitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Upper respiratory tract infection	1/9 (11.1%)		1/6 (16.7%)		1/6 (16.7%)		2/6 (33.3%)		1/6 (16.7%)		3/7 (42.9%)
Urinary tract infection	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Injury, poisoning and procedural complications
Ligament sprain	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Rib fracture	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Road traffic accident	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Traumatic haematoma	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Investigations
Alanine aminotransferase increased	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/7 (14.3%)
Aspartate aminotransferase increased	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		2/6 (33.3%)		1/7 (14.3%)
Blood potassium decreased	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Hepatic enzyme increased	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Urine analysis abnormal	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Weight decreased	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Metabolism and nutrition disorders
Decreased appetite	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Dyslipidaemia	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Hypercholesterolaemia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)
Hypertriglyceridaemia	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Hypokalaemia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/9 (33.3%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		2/6 (33.3%)		0/7 (0%)
Back pain	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)
Bursitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Intervertebral disc protrusion	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Musculoskeletal pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Myalgia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Neck pain	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Osteopenia	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Rheumatoid arthritis	2/9 (22.2%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastrointestinal tract adenoma	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Lung neoplasm	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Seborrhoeic keratosis	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Thyroid neoplasm	1/9 (11.1%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Nervous system disorders
Carpal tunnel syndrome	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Dizziness	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Headache	1/9 (11.1%)		0/6 (0%)		1/6 (16.7%)		3/6 (50%)		0/6 (0%)		1/7 (14.3%)
Paraesthesia	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Psychiatric disorders
Insomnia	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Renal and urinary disorders
Calculus ureteric	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Haematuria	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Nephrolithiasis	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Pyuria	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Renal cyst	0/9 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Reproductive system and breast disorders
Perineal pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Chronic obstructive pulmonary disease	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Cough	1/9 (11.1%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Dyspnoea	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Oropharyngeal pain	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		2/6 (33.3%)		0/7 (0%)
Rhinitis allergic	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Skin and subcutaneous tissue disorders
Alopecia	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		1/7 (14.3%)
Dermatitis	0/9 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/7 (14.3%)
Dermatitis contact	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Ingrowing nail	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/7 (0%)
Pruritus	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Rash	0/9 (0%)		0/6 (0%)		0/6 (0%)		1/6 (16.7%)		0/6 (0%)		0/7 (0%)
Skin ulcer	0/9 (0%)		1/6 (16.7%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Urticaria	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Vascular disorders
Haematoma	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Hypertension	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)
Orthostatic hypotension	1/9 (11.1%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/6 (0%)		0/7 (0%)

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.