Maraviroc in Rheumatoid Arthritis

• Sponsor: Pfizer (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00427934
• Collaborator: (none)
• Enrollment: 128
• Locations: 44
• Arms: 2
• Duration (Months): 20
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate whether maraviroc, an investigational drug given with methotrexate (MTX) is safe and effective in the treatment of rheumatoid arthritis in adult patients.

Condition or Disease	Intervention/Treatment	Phase
Arthritis, Rheumatoid	Drug: Maraviroc; Drug: Maraviroc Placebo	Phase 2

Detailed Description

Following a planned interim analysis in the POC component on 21 August 2008 by the internal DMC (Data Monitoring Committee) of study A4001056, the trial was discontinued due to lack of efficacy. All participating investigators/country offices and monitors were notified on 22 August 2008 to cease patient enrollment. The DMC indicated that maraviroc was well tolerated in the Rheumatoid Arthritis patients and there were no safety concerns in the study. The termination date of this trial was 07 October 2008 when the last patient last visit occurred.

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Assess the Safety and Efficacy of Maraviroc in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate
• Study Start Date: Feb 1, 2007
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Oct 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: 2	Drug: Maraviroc Placebo; Placebo tablets to match active drug. Two tablets are administered by mouth twice a day (BID) for 12 weeks.
Experimental: 1 This study was divided into two components: safety/pharmacokinetic (PK) and proof-of-concept (POC). In the safety/PK component either 150 mg or 300 mg tablets of maraviroc was administered twice a day (BID) to 16 rheumatoid arthritis subjects for 4 weeks.	Drug: Maraviroc; 300 mg (2- 150 mg tablets) are administered by mouth twice a day (BID) for 12 weeks.

Outcome Measures

Primary Outcome Measures

1. American College of Rheumatology (ACR) 20% Responders at Week 12 [Week 12]

   A subject was an ACR 20 responder if: the counts for both tender and swollen joints had reduced by 20% or more from baseline; and 3 out of the following 5 assessments showed reduction of 20% or more from baseline assessment: Patient's Assessment of Arthritis Pain (Visual Analogue Scale [VAS]), Patient's Global Assessment of Arthritis (VAS), Physician's Global Assessment of Arthritis (Categorical), Health Assessment Questionnaire - Disability Index (HAQ-DI), and C-Reactive Protein (CRP).

Secondary Outcome Measures

1. ACR 20% Responders at Weeks 1, 2, 4, and 8 [Weeks 1, 2, 4, and 8]

   A subject was an ACR 20 responder if: the counts for both tender and swollen joints had reduced by 20% or more from baseline; and 3 out of the following 5 assessments showed reduction of 20% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 20% data were collected, but not analyzed.

2. ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 [Weeks 1, 2, 4, 8, and 12]

   A subject was an ACR 50 responder if: the counts for both tender and swollen joints had reduced by 50% or more from baseline; and 3 out of the following 5 assessments showed reduction of 50% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 50% data were collected, but not analyzed.

3. ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 [Weeks 1, 2, 4, 8, and 12]

   A subject was an ACR 70 responder if: the counts for both tender and swollen joints had reduced by 70% or more from baseline; and 3 out of the following 5 assessments showed reduction of 70% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 70% data were collected, but not analyzed.

4. Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   Change from baseline at each visit was analyzed for tender/painful joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 tender/painful joint count data were collected, but not analyzed.

5. Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   Change from baseline at each visit was analyzed for swollen joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, MCP joints, PIP joints, and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 swollen joint count data were collected, but not analyzed.

6. Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   The severity of arthritis was scored by the subject between 0 (no pain) and 100 (most severe pain) on a 100 mm VAS. Change from baseline at each visit was analyzed for Patient's Assessment of Arthritis Pain. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Assessment of Arthritis Pain data were collected, but not analyzed.

7. Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   Subjects answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Subjects responded by using a 0 - 100 mm VAS where 0=very well and 100=very poorly. Change from baseline at each visit was analyzed for Patient's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Global Assessment of Arthritis Pain data were collected, but not analyzed.

8. Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   Physician's evaluation based on subject's disease signs, functional capacity and physical exam. Response recorded using 5-point scale: 1=Very Good, 2=Good, 3=Fair, 4=Poor and 5=Very Poor. Change from baseline at each visit was analyzed for Physician's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy thus Week 16 Physician's Global Assessment of Arthritis Pain data were collected but not analyzed.

9. Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

   HAQ-DI assesses degree of difficulty experienced in daily activity categories (dressing/grooming, arising, eating, walking, hygiene, reach, grip and other activities) over the past week. There are 20 questions and difficulty is scored from 0 (none), 1 (some), 2 (much) and 3 (unable to do). Scores were then averaged to give the disability index (scale of 0 to 3). Change from baseline at each visit was analyzed. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 HAQ-DI data were collected but not analyzed.

10. Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

    Change from baseline at each visit were analyzed for CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 CRP data were collected, but not analyzed.

11. Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 [Baseline, Weeks 1, 2, 4, 8, and 12]

    DAS28-4 (CRP) was calculated using the following formula: DAS28- 4(CRP) = 0.56 √28 Tender Joint Count + 0.28 √28 Swollen Joint Count + 0.36*natural logarithm(CRP + 1) + 0.014*Patient Global Assessment + 0.96. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity. Change from baseline at each visit was analyzed for DAS28-4 (CRP). The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 DAS28-4 (CRP) data were collected, but not analyzed.

12. Change From Baseline in Mean Orthostatic Blood Pressure (BP) [Baseline, 16 weeks]

    Supine BP was recorded after 5 minutes lying down; subjects then sat for 2 minutes then stood for 2 minutes and standing BP was recorded. Orthostatic BP = either a systolic BP drop > 20 mmHg, or diastolic BP drop > 10 mmHg and/or drop in systolic BP < 90 mmHg. If a subject met the orthostatic criteria, they were required to complete 2 additional readings to provide a triplicate reading. The means of replicate BP values were used in the analysis. Baseline = the latest non-missing value from a range of pre-treatment visits. Change from baseline to Week 16 was analyzed for orthostatic BP.

13. Change From Baseline in Mean Heart Rate [Baseline, 16 weeks]

    Heart rate = standing and supine at the same time the orthostatic BP measurements were obtained. Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were not used.

14. Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline [Baseline, 16 weeks]

    Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Maximum increase from baseline in supine and standing systolic BP was > = 30 mmHg, and maximum increase from baseline in supine and standing diastolic BP was > = 20 mmHg.

15. Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (RR Interval, PR Interval, QRS Complex, QT Interval, Corrected QT [QTc] Interval, QTcB Interval [Bazett's Correction], QTcF Interval [Fridericia's Correction]). [Baseline, 16 weeks]

    Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used. QTc interval was not measured for the PK populations.

16. Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). [Baseline, 16 weeks]

    Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used.

17. Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline [Baseline, 16 weeks]

    Maximum QTcB, QTcF, and QTc intervals were defined as 450 to < 480 msec, 480 to < 500 msec, or > = 500 msec.

18. Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 [Baseline, Weeks 4 and 12]

    The SF-36 v.2 (Acute version) is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (physical component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.

19. Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 [Baseline, Weeks 4 and 12]

    The SF-36 v.2 (Acute version) [12] is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (mental component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.

20. Number of Subjects With Withdrawal From Study Due to Lack of Efficacy [16 weeks]

    Withdrawal is the total number of withdrawals from the study. Withdrawal due to lack of efficacy was collected based on the investigator's judgement.

21. Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. [Weeks 1 to 12]

    Withdrawal due to lack of efficacy was collected based on the investigator's judgement. Time to withdrawal was measured by the probability that a subject did not withdraw due to lack of efficacy by a particular visit. This was a statistical estimate (Kaplan-Meier Survival Analysis) of the probability that a participant would not withdraw due to lack of efficacy.

22. Area Under the Plasma Concentration-Time Profile From Time Zero to Four Hours Postdose (AUC 0-4) for MTX at Screening and Week 1 and Maraviroc at Week 1 [Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)]

    Effect of maraviroc on the PK of MTX (comparison of AUC0-4 of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).

23. Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 [Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)]

    Effect of maraviroc on the PK of MTX (comparison of Cmax of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).

24. Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 [Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)]

    PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Must be legal age of consent

• Must have active rheumatoid arthritis based upon the American College of Rheumatology (ACR) 1987 (Revised Criteria); minimum disease criteria required for entry into the efficacy component of the study

• Must meet ACR 1991 Revised Criteria for Global Functional Status in RA, Class I, II, or III

• Must be receiving methotrexate for at least 12 weeks duration and on a stable dose for 4 weeks.

Exclusion Criteria:

• Diagnosed with any other inflammatory arthritis or a secondary non-inflammatory arthritis that would interfere with disease activity assessments.

• Subject receiving prior treatment with certain medications for rheumatoid arthritis

• Tuberculosis and/or a positive tuberculin reaction

• Significant trauma or major surgery within 2 months

• History of alcohol and/or drug abuse outside of a defined period of abstinence

• History of or a finding at screening of postural hypotension

• Any condition that would affect the oral absorption of the drug

• History of cancer and in remission less than 3 years or Grade III-IV congestive heart failure

• Having an infection of human immunodeficiency virus (HIV), Hepatitis B or C or evidence of any active infection

• Abnormalities of clinical or laboratory assessments completed at the screening visit such as elevated liver enzymes, decreased hemoglobin or an abnormal ECG

• Having a positive chemokine receptor 5 (CCR5) delta 32 mutation

• Requiring the use of certain medications

• Lactating or pregnant women or subjects have reproductive potential unwilling to use an adequate method of birth control

• Chronic or recent serious or life-threatening infection; severe , progressive and/or uncontrollable renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological disease within 12 weeks of the first dose.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pfizer Investigational Site	Huntington Beach	California	United States	92646
2	Pfizer Investigational Site	San Francisco	California	United States	94115
3	Pfizer Investigational Site	Hamden	Connecticut	United States	06518
4	Pfizer Investigational Site	Meriden	Connecticut	United States	06450
5	Pfizer Investigational Site	New Haven	Connecticut	United States	06510-2716
6	Pfizer Investigational Site	New Haven	Connecticut	United States	06511-5473
7	Pfizer Investigational Site	Daytona Beach	Florida	United States	32114
8	Pfizer Investigational Site	Port Orange	Florida	United States	32127
9	Pfizer Investigational Site	Savannah	Georgia	United States	31405
10	Pfizer Investigational Site	Savannah	Georgia	United States	31406
11	Pfizer Investigational Site	Moline	Illinois	United States	61265
12	Pfizer Investigational Site	Madisonville	Kentucky	United States	42431
13	Pfizer Investigational Site	Kalamazoo	Michigan	United States	49007
14	Pfizer Investigational Site	Kalamazoo	Michigan	United States	49048
15	Pfizer Investigational Site	Omaha	Nebraska	United States	68154
16	Pfizer Investigational Site	Las Vegas	Nevada	United States	89128
17	Pfizer Investigational Site	Syracuse	New York	United States	13210
18	Pfizer Investigational Site	Hickory	North Carolina	United States	28601
19	Pfizer Investigational Site	Hickory	North Carolina	United States	28602
20	Pfizer Investigational Site	Minot	North Dakota	United States	58701
21	Pfizer Investigational Site	Duncansville	Pennsylvania	United States	16635
22	Pfizer Investigational Site	Maroochydore	Queensland	Australia	4558
23	Pfizer Investigational Site	Woodville	South Australia	Australia	5011
24	Pfizer Investigational Site	Hobart	Tasmania	Australia	7001
25	Pfizer Investigational Site	Berlin		Germany	10117
26	Pfizer Investigational Site	Berlin		Germany	14059
27	Pfizer Investigational Site	Leipzig		Germany	04103
28	Pfizer Investigational Site	Hyderabad	Andhra Pradesh	India	500 082
29	Pfizer Investigational Site	Bangalore	Karnataka	India	560 034
30	Pfizer Investigational Site	Bangalore	Karnataka	India	560003
31	Pfizer Investigational Site	Genova		Italy	16132
32	Pfizer Investigational Site	Pavia		Italy	27100
33	Pfizer Investigational Site	Guadalajara	Jalisco	Mexico	44690
34	Pfizer Investigational Site	Guadalajara	Jalisco	Mexico	CP 44340
35	Pfizer Investigational Site	Coimbra		Portugal	3000-075
36	Pfizer Investigational Site	Lisboa		Portugal	1600-035
37	Pfizer Investigational Site	Lisbon		Portugal	1000-247
38	Pfizer Investigational Site	Santiago de Compostela	A Coruña	Spain	15705
39	Pfizer Investigational Site	Barcelona		Spain	08035
40	Pfizer Investigational Site	Madrid		Spain	28007
41	Pfizer Investigational Site	Sevilla		Spain	41014
42	Pfizer Investigational Site	Dnipropetrovsk		Ukraine	49005
43	Pfizer Investigational Site	Kharkiv		Ukraine	61000
44	Pfizer Investigational Site	Simferopol		Ukraine	95017

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.

• ClinicalTrials.gov Identifier: NCT00427934
• Other Study ID Numbers: A4001056
• First Posted: Jan 29, 2007
• Last Update Posted: Nov 5, 2014
• Last Verified: Oct 1, 2014

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Maraviroc

Study Results

Participant Flow

Arm/Group Title	Maraviroc 150 mg BID (Pharmacokinetic [PK])	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (Proof-of-Concept [POC])	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth twice a day (BID) for 4 weeks with stable weekly doses of methotrexate (MTX).	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Period Title: Overall Study
STARTED	8	8	78	34
Treated	8	8	77	33
COMPLETED	7	8	55	19
NOT COMPLETED	1	0	23	15

Baseline Characteristics

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)	Total
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Total of all reporting groups
Overall Participants	8	8	77	33	126
Age, Customized (Number) [Number]
< 18 years	0 0%	0 0%	0 0%	0 0%	0 0%
18 to 44 years	1 12.5%	0 0%	15 19.5%	6 18.2%	22 17.5%
45 to 64 years	4 50%	8 100%	48 62.3%	21 63.6%	81 64.3%
> = 65 years	3 37.5%	0 0%	14 18.2%	6 18.2%	23 18.3%
Sex: Female, Male (Count of Participants)
Female	4 50%	5 62.5%	71 92.2%	22 66.7%	102 81%
Male	4 50%	3 37.5%	6 7.8%	11 33.3%	24 19%

Outcome Measures

1. Secondary Outcome

Title	ACR 20% Responders at Weeks 1, 2, 4, and 8
Description	A subject was an ACR 20 responder if: the counts for both tender and swollen joints had reduced by 20% or more from baseline; and 3 out of the following 5 assessments showed reduction of 20% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 20% data were collected, but not analyzed.
Time Frame	Weeks 1, 2, 4, and 8

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	8 100%	4 50%
Week 2	12 150%	5 62.5%
Week 4	21 262.5%	8 100%
Week 8	23 287.5%	7 87.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.790
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-1.73
	Confidence Interval	() 90%; -15.13 to 8.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.477
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.43
	Confidence Interval	() 90%; -13.67 to 11.64
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.370
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	3.03
	Confidence Interval	() 90%; -12.85 to 16.77
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.175
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	8.66
	Confidence Interval	() 90%; -7.07 to 22.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

2. Secondary Outcome

Title	ACR 50% Responders at Weeks 1, 2, 4, 8, and 12
Description	A subject was an ACR 50 responder if: the counts for both tender and swollen joints had reduced by 50% or more from baseline; and 3 out of the following 5 assessments showed reduction of 50% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 50% data were collected, but not analyzed.
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	1 12.5%	0 0%
Week 2	2 25%	0 0%
Week 4	2 25%	2 25%
Week 8	6 75%	3 37.5%
Week 12	8 100%	3 37.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.420
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.30
	Confidence Interval	() 90%; -6.34 to 6.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	2.60
	Confidence Interval	() 90%; -5.08 to 7.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-3.46
	Confidence Interval	() 90%; -14.39 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.899
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-1.30
	Confidence Interval	() 90%; -13.56 to 7.92
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.489
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	1.30
	Confidence Interval	() 90%; -11.24 to 10.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

3. Secondary Outcome

Title	ACR 70% Responders at Weeks 1, 2, 4, 8, and 12
Description	A subject was an ACR 70 responder if: the counts for both tender and swollen joints had reduced by 70% or more from baseline; and 3 out of the following 5 assessments showed reduction of 70% or more from baseline assessment: Patient's Assessment of Arthritis Pain, Patient's Global Assessment of Arthritis, Physician's Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 70% data were collected, but not analyzed.
Time Frame	Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	0 0%	0 0%
Week 2	0 0%	0 0%
Week 4	0 0%	1 12.5%
Week 8	2 25%	0 0%
Week 12	0 0%	1 12.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-3.03
	Confidence Interval	() 90%; -13.59 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.258
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	2.60
	Confidence Interval	() 90%; -5.08 to 7.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	-3.03
	Confidence Interval	() 90%; -13.59 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

4. Secondary Outcome

Title	Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12
Description	Change from baseline at each visit was analyzed for tender/painful joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 tender/painful joint count data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	-0.81 (0.68)	-1.91 (0.96)
Week 2	-2.08 (0.76)	-2.38 (1.08)
Week 4	-4.00 (0.84)	-4.01 (1.20)
Week 8	-4.85 (0.85)	-3.24 (1.21)
Week 12	-4.89 (0.84)	-3.41 (1.19)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.335
	Comments	This analysis was carried out using analysis of covariance (ANCOVA) with baseline tender/painful joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.10
	Confidence Interval	() 90%; -0.79 to 2.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments	This analysis was carried out using ANCOVA with baseline tender/painful joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.30
	Confidence Interval	() 90%; -1.82 to 2.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments	This analysis was carried out using ANCOVA with baseline tender/painful joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	() 90%; -2.35 to 2.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.263
	Comments	This analysis was carried out using ANCOVA with baseline tender/painful joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.61
	Confidence Interval	() 90%; -3.98 to 0.76
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.294
	Comments	This analysis was carried out using ANCOVA with baseline tender/painful joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.48
	Confidence Interval	() 90%; -3.82 to 0.85
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12
Description	Change from baseline at each visit was analyzed for swollen joint count. Twenty-eight tender and swollen joint scores included the same joints: shoulders, elbows, wrists, MCP joints, PIP joints, and the knees. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 swollen joint count data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	-1.39 (0.49)	-1.07 (0.70)
Week 2	-2.25 (0.61)	-2.51 (0.87)
Week 4	-3.93 (0.54)	-4.08 (0.77)
Week 8	-4.48 (0.62)	-3.03 (0.88)
Week 12	-3.48 (0.66)	-3.43 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.700
	Comments	This analysis was carried out using ANCOVA baseline swollen joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.32
	Confidence Interval	() 90%; -1.70 to 1.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.799
	Comments	This analysis was carried out using ANCOVA baseline swollen joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.26
	Confidence Interval	() 90%; -1.45 to 1.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.867
	Comments	This analysis was carried out using ANCOVA baseline swollen joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.15
	Confidence Interval	() 90%; -1.35 to 1.66
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.167
	Comments	This analysis was carried out using ANCOVA baseline swollen joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.45
	Confidence Interval	() 90%; -3.17 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.966
	Comments	This analysis was carried out using ANCOVA baseline swollen joint count as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.05
	Confidence Interval	() 90%; -1.91 to 1.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
Description	The severity of arthritis was scored by the subject between 0 (no pain) and 100 (most severe pain) on a 100 mm VAS. Change from baseline at each visit was analyzed for Patient's Assessment of Arthritis Pain. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Assessment of Arthritis Pain data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1	-3.96 (2.18)	-3.62 (3.10)
Week 2	-8.46 (2.65)	-3.20 (3.77)
Week 4	-8.35 (2.70)	-9.08 (3.85)
Week 8	-10.30 (2.98)	-8.67 (4.24)
Week 12	-8.30 (2.85)	-6.09 (4.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.925
	Comments	This analysis was carried out using ANCOVA with baseline patient's assessment of arthritis pain as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.34
	Confidence Interval	() 90%; -6.41 to 5.72
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.239
	Comments	This analysis was carried out using ANCOVA with baseline patient's assessment of arthritis pain as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.26
	Confidence Interval	() 90%; -12.62 to 2.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.872
	Comments	This analysis was carried out using ANCOVA with baseline patient's assessment of arthritis pain as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.73
	Confidence Interval	() 90%; -6.79 to 8.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.745
	Comments	This analysis was carried out using ANCOVA with baseline patient's assessment of arthritis pain as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.63
	Confidence Interval	() 90%; -9.91 to 6.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.644
	Comments	This analysis was carried out using ANCOVA with baseline patient's assessment of arthritis pain as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.22
	Confidence Interval	() 90%; -10.14 to 5.71
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
Description	Subjects answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Subjects responded by using a 0 - 100 mm VAS where 0=very well and 100=very poorly. Change from baseline at each visit was analyzed for Patient's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 Patient's Global Assessment of Arthritis Pain data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	76	33
Week 1	-4.70 (2.22)	-2.34 (3.13)
Week 2	-8.85 (2.48)	-4.88 (3.49)
Week 4	-10.00 (2.74)	-9.02 (3.86)
Week 8	-11.12 (2.93)	-3.44 (4.13)
Week 12	-8.55 (2.88)	-6.78 (4.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.524
	Comments	This analysis was carried out using ANCOVA with baseline Patient's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.36
	Confidence Interval	() 90%; -8.49 to 3.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.338
	Comments	This analysis was carried out using ANCOVA with baseline Patient's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.96
	Confidence Interval	() 90%; -10.80 to 2.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.830
	Comments	This analysis was carried out using ANCOVA with baseline Patient's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.98
	Confidence Interval	() 90%; -8.55 to 6.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.118
	Comments	This analysis was carried out using ANCOVA with baseline Patient's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.68
	Confidence Interval	() 90%; -15.76 to 0.40
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.712
	Comments	This analysis was carried out using ANCOVA with baseline Patient's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.78
	Confidence Interval	() 90%; -9.73 to 6.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12
Description	Physician's evaluation based on subject's disease signs, functional capacity and physical exam. Response recorded using 5-point scale: 1=Very Good, 2=Good, 3=Fair, 4=Poor and 5=Very Poor. Change from baseline at each visit was analyzed for Physician's Global Assessment. The Week 16 visit (follow-up) was designed for safety rather than efficacy thus Week 16 Physician's Global Assessment of Arthritis Pain data were collected but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	75	32
Week 1	-0.30 (0.08)	-0.22 (0.11)
Week 2	-0.44 (0.09)	-0.39 (0.12)
Week 4	-0.49 (0.10)	-0.44 (0.13)
Week 8	-0.63 (0.10)	-0.37 (0.14)
Week 12	-0.49 (0.11)	-0.36 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.540
	Comments	This analysis was carried out using ANCOVA with baseline Physician's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	() 90%; -0.28 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.757
	Comments	This analysis was carried out using ANCOVA with baseline Physician's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.04
	Confidence Interval	() 90%; -0.28 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.767
	Comments	This analysis was carried out using ANCOVA with baseline Physician's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.05
	Confidence Interval	() 90%; -0.31 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.112
	Comments	This analysis was carried out using ANCOVA with baseline Physician's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.26
	Confidence Interval	() 90%; -0.52 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.490
	Comments	This analysis was carried out using ANCOVA with baseline Physician's Global Assessment of Arthritis as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	() 90%; -0.42 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12
Description	HAQ-DI assesses degree of difficulty experienced in daily activity categories (dressing/grooming, arising, eating, walking, hygiene, reach, grip and other activities) over the past week. There are 20 questions and difficulty is scored from 0 (none), 1 (some), 2 (much) and 3 (unable to do). Scores were then averaged to give the disability index (scale of 0 to 3). Change from baseline at each visit was analyzed. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 HAQ-DI data were collected but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	31
Week 1	-0.08 (0.05)	-0.03 (0.07)
Week 2	-0.22 (0.06)	-0.04 (0.08)
Week 4	-0.24 (0.06)	-0.18 (0.09)
Week 8	-0.25 (0.07)	-0.03 (0.10)
Week 12	-0.18 (0.08)	-0.06 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.464
	Comments	This analysis was carried out using ANCOVA with HAQ-DI as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	() 90%; -0.19 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments	This analysis was carried out using ANCOVA with HAQ-DI as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.18
	Confidence Interval	() 90%; -0.35 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.532
	Comments	This analysis was carried out using ANCOVA with HAQ-DI as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.06
	Confidence Interval	() 90%; -0.23 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.063
	Comments	This analysis was carried out using ANCOVA with HAQ-DI as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.22
	Confidence Interval	() 90%; -0.41 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.396
	Comments	This analysis was carried out using ANCOVA with HAQ-DI as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.12
	Confidence Interval	() 90%; -0.36 to 0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12
Description	Change from baseline at each visit were analyzed for CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 CRP data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	73	31
Week 1	1.20 (1.87)	3.40 (2.67)
Week 2	3.14 (2.06)	1.81 (2.93)
Week 4	3.36 (2.34)	-1.30 (3.33)
Week 8	2.33 (2.10)	-1.14 (2.98)
Week 12	2.35 (2.26)	1.93 (3.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.481
	Comments	This analysis was carried out using ANCOVA with CRP as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.20
	Confidence Interval	() 90%; -7.36 to 2.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.698
	Comments	This analysis was carried out using ANCOVA with CRP as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.33
	Confidence Interval	() 90%; -4.34 to 6.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.233
	Comments	This analysis was carried out using ANCOVA with CRP as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.65
	Confidence Interval	() 90%; -1.79 to 11.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.320
	Comments	This analysis was carried out using ANCOVA with CRP as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.48
	Confidence Interval	() 90%; -2.29 to 9.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.912
	Comments	This analysis was carried out using ANCOVA with CRP as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.41
	Confidence Interval	() 90%; -5.81 to 6.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Description	DAS28-4 (CRP) was calculated using the following formula: DAS28- 4(CRP) = 0.56 √28 Tender Joint Count + 0.28 √28 Swollen Joint Count + 0.36*natural logarithm(CRP + 1) + 0.014*Patient Global Assessment + 0.96. DAS28 provides a number on a scale (0 to 10) indicating current disease activity. A score above 5.1 means high disease activity and a score below 3.2 indicates low disease activity. Change from baseline at each visit was analyzed for DAS28-4 (CRP). The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 DAS28-4 (CRP) data were collected, but not analyzed.
Time Frame	Baseline, Weeks 1, 2, 4, 8, and 12

Outcome Measure Data

Analysis Population Description

FAS. Missing values were imputed by the method of LOCF.

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	72	31
Week 1	-0.23 (0.09)	-0.17 (0.13)
Week 2	-0.41 (0.12)	-0.33 (0.17)
Week 4	-0.64 (0.14)	-0.65 (0.19)
Week 8	-0.82 (0.15)	-0.51 (0.21)
Week 12	-0.73 (0.16)	-0.63 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 1
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.653
	Comments	This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.07
	Confidence Interval	() 90%; -0.31 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 2
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.703
	Comments	This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.08
	Confidence Interval	() 90%; -0.41 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.968
	Comments	This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.01
	Confidence Interval	() 90%; -0.37 to 0.39
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 8
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments	This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.31
	Confidence Interval	() 90%; -0.72 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.696
	Comments	This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.10
	Confidence Interval	() 90%; -0.53 to 0.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change From Baseline in Mean Orthostatic Blood Pressure (BP)
Description	Supine BP was recorded after 5 minutes lying down; subjects then sat for 2 minutes then stood for 2 minutes and standing BP was recorded. Orthostatic BP = either a systolic BP drop > 20 mmHg, or diastolic BP drop > 10 mmHg and/or drop in systolic BP < 90 mmHg. If a subject met the orthostatic criteria, they were required to complete 2 additional readings to provide a triplicate reading. The means of replicate BP values were used in the analysis. Baseline = the latest non-missing value from a range of pre-treatment visits. Change from baseline to Week 16 was analyzed for orthostatic BP.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
Standing Systolic BP	20.9 (13.18)	18.0 (7.71)	17.8 (11.25)	17.5 (12.36)
Supine Systolic BP	20.9 (13.58)	18.3 (9.51)	17.5 (13.86)	18.0 (11.12)
Standing Diastolic BP	13.0 (4.97)	8.3 (5.65)	11.7 (6.98)	11.5 (5.15)
Supine Diastolic BP	10.3 (7.94)	10.9 (5.08)	12.2 (8.14)	10.8 (5.12)

13. Primary Outcome

Title	American College of Rheumatology (ACR) 20% Responders at Week 12
Description	A subject was an ACR 20 responder if: the counts for both tender and swollen joints had reduced by 20% or more from baseline; and 3 out of the following 5 assessments showed reduction of 20% or more from baseline assessment: Patient's Assessment of Arthritis Pain (Visual Analogue Scale [VAS]), Patient's Global Assessment of Arthritis (VAS), Physician's Global Assessment of Arthritis (Categorical), Health Assessment Questionnaire - Disability Index (HAQ-DI), and C-Reactive Protein (CRP).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) was defined as an intent-to-treat analysis set that included all subjects randomized to treatment who had taken at least 1 dose of study medication. Missing values were imputed by the method of last observation carried forward (LOCF).

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Number [Participants]	21 262.5%	6 75%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments	p-value (one-sided) was based on Barnard exact test if more than 20% of expected cell counts were < 5 otherwise Pearson chi-square test.
	Method	Barnard/Pearson chi-square test
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	9.09
	Confidence Interval	() 90%; -6.16 to 21.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

14. Secondary Outcome

Title	Change From Baseline in Mean Heart Rate
Description	Heart rate = standing and supine at the same time the orthostatic BP measurements were obtained. Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were not used.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
Standing Heart Rate	14.6 (6.73)	8.1 (3.64)	11.8 (6.91)	11.4 (8.13)
Supine Heart Rate	15.0 (8.28)	10.4 (4.56)	11.6 (6.06)	9.2 (6.16)

15. Secondary Outcome

Title	Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline
Description	Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Maximum increase from baseline in supine and standing systolic BP was > = 30 mmHg, and maximum increase from baseline in supine and standing diastolic BP was > = 20 mmHg.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
Maximum Increase in Supine Systolic BP	2 25%	1 12.5%	4 5.2%	3 9.1%
Maximum Increase in Standing Systolic BP	1 12.5%	1 12.5%	2 2.6%	2 6.1%
Maximum Increase in Supine Diastolic BP	1 12.5%	1 12.5%	8 10.4%	0 0%
Maximum Increase in Standing Diastolic BP	0 0%	0 0%	3 3.9%	2 6.1%

16. Secondary Outcome

Title	Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (RR Interval, PR Interval, QRS Complex, QT Interval, Corrected QT [QTc] Interval, QTcB Interval [Bazett's Correction], QTcF Interval [Fridericia's Correction]).
Description	Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used. QTc interval was not measured for the PK populations.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
RR Interval	137.0 (79.18)	114.3 (63.38)	140.0 (70.81)	117.6 (48.26)
PR Interval	19.7 (7.13)	13.0 (6.93)	16.2 (8.00)	15.4 (10.47)
QRS Complex	7.6 (4.75)	7.3 (4.89)	11.3 (6.56)	10.2 (5.35)
QT Interval	35.0 (19.47)	22.5 (10.67)	31.9 (18.74)	28.7 (13.97)
QTc Interval	0 (0)	0 (0)	19.6 (17.69)	20.3 (12.75)
QTcB Interval	23.1 (19.70)	23.3 (9.55)	27.9 (18.47)	30.2 (23.88)
QTcF Interval	22.9 (19.64)	17.3 (7.16)	28.3 (18.77)	29.8 (22.20)

17. Secondary Outcome

Title	Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate).
Description	Baseline was defined to be the latest non-missing value from a range of pre-treatment visits. Means of replicate values were used.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
Mean (Standard Deviation) [bpm]	11.2 (5.82)	8.8 (5.76)	12.0 (6.40)	10.5 (4.91)

18. Secondary Outcome

Title	Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline
Description	Maximum QTcB, QTcF, and QTc intervals were defined as 450 to < 480 msec, 480 to < 500 msec, or > = 500 msec.
Time Frame	Baseline, 16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	8	8	77	33
Maximum QTc Interval 450 to < 480 msec	0 0%	0 0%	2 2.6%	2 6.1%
Maximum QTc Interval 480 to < 500 msec	0 0%	0 0%	0 0%	0 0%
Maximum QTc Interval > = 500 msec	0 0%	0 0%	0 0%	0 0%
Maximum QTcB Interval 450 to < 480 msec	1 12.5%	3 37.5%	13 16.9%	8 24.2%
Maximum QTcB Interval 480 to < 500 msec	0 0%	0 0%	2 2.6%	1 3%
Maximum QTcB Interval > = 500 msec	0 0%	0 0%	0 0%	1 3%
Maximum QTcF Interval 450 to < 480 msec	0 0%	2 25%	9 11.7%	5 15.2%
Maximum QTcF Interval 480 to < 500 msec	0 0%	0 0%	0 0%	0 0%
Maximum QTcF Interval > = 500 msec	0 0%	0 0%	0 0%	0 0%

19. Secondary Outcome

Title	Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12
Description	The SF-36 v.2 (Acute version) is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (physical component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.
Time Frame	Baseline, Weeks 4 and 12

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	69	30
Week 4	4.33 (0.89)	3.76 (1.25)
Week 12	3.14 (1.04)	4.81 (1.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.698
	Comments	This analysis was carried out ANCOVA with baseline SF-36 score as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.57
	Confidence Interval	() 90%; -1.87 to 3.01
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.344
	Comments	This analysis was carried out ANCOVA with baseline SF-36 score as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.68
	Confidence Interval	() 90%; -4.62 to 1.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12
Description	The SF-36 v.2 (Acute version) [12] is a 36-item generic health status measure that measures 8 general health concepts: Physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Each domain of the eight domains and the summary concept (mental component score) are scored to yield values between 0 (worst) and 100 (best). Change from baseline at Weeks 4 and 12 were analyzed for SF-36. Due to the termination of the study, SF-36 results for the PK component group were not analyzed.
Time Frame	Baseline, Weeks 4 and 12

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	69	30
Week 4	1.42 (1.25)	0.72 (1.75)
Week 12	1.17 (1.41)	0.61 (2.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 4
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.734
	Comments	This analysis was carried out ANCOVA with baseline SF-36 score as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.70
	Confidence Interval	() 90%; -2.71 to 4.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments	Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.818
	Comments	This analysis was carried out ANCOVA with baseline SF-36 score as the covariate, treatment, region as fixed effects.
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.56
	Confidence Interval	() 90%; -3.50 to 4.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

21. Secondary Outcome

Title	Number of Subjects With Withdrawal From Study Due to Lack of Efficacy
Description	Withdrawal is the total number of withdrawals from the study. Withdrawal due to lack of efficacy was collected based on the investigator's judgement.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Overall Withdrawal	22 275%	14 175%
Withdrawal due to Lack of Efficacy	5 62.5%	2 25%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.649
	Comments
	Method	Fisher Exact
	Comments

22. Secondary Outcome

Title	Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy.
Description	Withdrawal due to lack of efficacy was collected based on the investigator's judgement. Time to withdrawal was measured by the probability that a subject did not withdraw due to lack of efficacy by a particular visit. This was a statistical estimate (Kaplan-Meier Survival Analysis) of the probability that a participant would not withdraw due to lack of efficacy.
Time Frame	Weeks 1 to 12

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Maraviroc 300 mg BID (POC)	Placebo (POC)
Arm/Group Description	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Measure Participants	77	33
Week 1 (n=77, 33)	1.00	1.00
Week 2 (n=77, 32)	1.00	1.00
Week 4 (n=76, 32)	1.00	1.00
Week 8 (n=69, 31)	0.99	1.00
Week 12 (n=58, 21)	0.93	0.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Maraviroc 300 mg BID (POC), Placebo (POC)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9826
	Comments
	Method	Log Rank
	Comments

23. Secondary Outcome

Title	Area Under the Plasma Concentration-Time Profile From Time Zero to Four Hours Postdose (AUC 0-4) for MTX at Screening and Week 1 and Maraviroc at Week 1
Description	Effect of maraviroc on the PK of MTX (comparison of AUC0-4 of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Time Frame	Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)

Outcome Measure Data

Analysis Population Description

All available PK data from the Safety/PK Component were included.

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Measure Participants	8	8
Plasma MTX (Screening)	909.4 (422.37)	888.9 (249.51)
Plasma MTX (Week 1)	1045.6 (329.93)	844.8 (273.92)
Plasma Maraviroc (Week 1)	451.6 (247.33)	1106.8 (1029.60)

24. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1
Description	Effect of maraviroc on the PK of MTX (comparison of Cmax of MTX at screening versus at Week 1 after coadministration with 150 mg or 300 mg of maraviroc). PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Time Frame	Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)

Outcome Measure Data

Analysis Population Description

All available PK data from the Safety/PK Component were included.

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Measure Participants	8	8
Plasma MTX (Screening)	338.7 (143.94)	352.1 (115.72)
Plasma MTX (Week 1)	403.8 (97.46)	322.8 (104.20)
Plasma Maraviroc (Week 1)	199.59 (115.603)	461.03 (365.715)

25. Secondary Outcome

Title	Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1
Description	PK was assessed at screening (MTX) and at Week 1 (maraviroc and MTX).
Time Frame	Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose)

Outcome Measure Data

Analysis Population Description

All available PK data from the Safety/PK Component were included.

Arm/Group Title	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Measure Participants	8	8
Plasma MTX (Screening)	2.000	1.000
Plasma MTX (Week 1)	1.000	1.500
Plasma Maraviroc (Week 1)	2.000	2.500

Adverse Events

Arm/Group Title	Maraviroc 150 mg BID (PK)		Maraviroc 300 mg BID (PK)		Maraviroc 300 mg BID (POC)		Placebo (POC)
Arm/Group Description	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.		300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.		300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.		Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
All Cause Mortality
	Maraviroc 150 mg BID (PK)		Maraviroc 300 mg BID (PK)		Maraviroc 300 mg BID (POC)		Placebo (POC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Maraviroc 150 mg BID (PK)		Maraviroc 300 mg BID (PK)		Maraviroc 300 mg BID (POC)		Placebo (POC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/8 (0%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Other (Not Including Serious) Adverse Events
	Maraviroc 150 mg BID (PK)		Maraviroc 300 mg BID (PK)		Maraviroc 300 mg BID (POC)		Placebo (POC)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/8 (50%)		4/8 (50%)		39/77 (50.6%)		21/33 (63.6%)
Blood and lymphatic system disorders
Anaemia	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Lymphopenia	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Neutropenia	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Cardiac disorders
Atrial fibrillation	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Ear and labyrinth disorders
Tinnitus	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Endocrine disorders
Goitre	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Eye disorders
Conjunctivitis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		1/33 (3%)
Diplopia	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Glaucoma	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Vision blurred	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Visual acuity reduced	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Visual impairment	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Gastrointestinal disorders
Abdominal pain upper	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Constipation	0/8 (0%)		0/8 (0%)		6/77 (7.8%)		0/33 (0%)
Diarrhoea	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		2/33 (6.1%)
Dry mouth	0/8 (0%)		1/8 (12.5%)		1/77 (1.3%)		1/33 (3%)
Dyspepsia	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		0/33 (0%)
Flatulence	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Nausea	1/8 (12.5%)		0/8 (0%)		4/77 (5.2%)		0/33 (0%)
Rectal haemorrhage	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Stomatitis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Abnormal faeces	0/8 (0%)		1/8 (12.5%)		0/77 (0%)		0/33 (0%)
General disorders
Chest pain	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Chills	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		1/33 (3%)
Fatigue	1/8 (12.5%)		0/8 (0%)		3/77 (3.9%)		0/33 (0%)
Feeling cold	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Irritability	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Oedema peripheral	0/8 (0%)		0/8 (0%)		0/77 (0%)		2/33 (6.1%)
Pyrexia	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		0/33 (0%)
Ulcer	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Influenza like illness	0/8 (0%)		1/8 (12.5%)		0/77 (0%)		0/33 (0%)
Immune system disorders
Seasonal allergy	0/8 (0%)		1/8 (12.5%)		0/77 (0%)		0/33 (0%)
Infections and infestations
Bronchitis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Gastroenteritis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Influenza	0/8 (0%)		0/8 (0%)		0/77 (0%)		2/33 (6.1%)
Nasopharyngitis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Oral herpes	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Respiratory tract infection	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		0/33 (0%)
Sinusitis	0/8 (0%)		1/8 (12.5%)		0/77 (0%)		1/33 (3%)
Upper respiratory tract infection	0/8 (0%)		1/8 (12.5%)		3/77 (3.9%)		0/33 (0%)
Viral upper respiratory tract infection	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		1/33 (3%)
Injury, poisoning and procedural complications
Bite	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Humerus fracture	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Back injury	1/8 (12.5%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Investigations
Alanine aminotransferase increased	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Blood bilirubin increased	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Blood creatinine increased	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Metabolism and nutrition disorders
Hypertriglyceridaemia	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/8 (25%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Bursitis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Muscle spasms	1/8 (12.5%)		1/8 (12.5%)		0/77 (0%)		1/33 (3%)
Musculoskeletal chest pain	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Myalgia	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		1/33 (3%)
Rheumatoid arthritis	0/8 (0%)		0/8 (0%)		3/77 (3.9%)		8/33 (24.2%)
Arthritis	1/8 (12.5%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Back pain	1/8 (12.5%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Flank pain	0/8 (0%)		1/8 (12.5%)		0/77 (0%)		0/33 (0%)
Musculoskeletal pain	1/8 (12.5%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Pain in extremity	1/8 (12.5%)		0/8 (0%)		0/77 (0%)		0/33 (0%)
Nervous system disorders
Dizziness	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		1/33 (3%)
Headache	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		1/33 (3%)
Sciatica	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Sinus headache	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Somnolence	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Psychiatric disorders
Anxiety	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Depression	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Hallucination, olfactory	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Mood swings	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Sleep disorder	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Renal and urinary disorders
Micturition urgency	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Nephrolithiasis	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Pollakiuria	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Dyspnoea	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Nasal congestion	0/8 (0%)		1/8 (12.5%)		1/77 (1.3%)		1/33 (3%)
Oropharyngeal pain	0/8 (0%)		1/8 (12.5%)		1/77 (1.3%)		0/33 (0%)
Rhinorrhoea	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Skin and subcutaneous tissue disorders
Cold sweat	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Purpura	0/8 (0%)		0/8 (0%)		0/77 (0%)		1/33 (3%)
Vascular disorders
Hot flush	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Hypotension	0/8 (0%)		0/8 (0%)		1/77 (1.3%)		0/33 (0%)
Orthostatic hypotension	0/8 (0%)		0/8 (0%)		2/77 (2.6%)		0/33 (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 < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.