Arthritis, Rheumatoid
Conditions
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.
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.
Interventions
DRUGMaraviroc
300 mg (2- 150 mg tablets) are administered by mouth twice a day (BID) for 12 weeks.
Placebo tablets to match active drug. Two tablets are administered by mouth twice a day (BID) for 12 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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. |
Countries
Australia, Germany, India, Italy, Mexico, Portugal, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc 150 mg BID (PK) 150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX. | 8 |
| Maraviroc 300 mg BID (PK) 300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX. | 8 |
| Maraviroc 300 mg BID (POC) 300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX. | 77 |
| Placebo (POC) Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX. | 33 |
| Total | 126 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 5 | 4 |
| Overall Study | Lack of Efficacy | 0 | 0 | 5 | 2 |
| Overall Study | Other | 0 | 0 | 11 | 5 |
| Overall Study | Randomized But Did Not Receive Treatment | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | Maraviroc 150 mg BID (PK) | Maraviroc 300 mg BID (PK) | Maraviroc 300 mg BID (POC) | Placebo (POC) | Total |
|---|---|---|---|---|---|
| Age, Customized 18 to 44 years | 1 Participants | 0 Participants | 15 Participants | 6 Participants | 22 Participants |
| Age, Customized < 18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 45 to 64 years | 4 Participants | 8 Participants | 48 Participants | 21 Participants | 81 Participants |
| Age, Customized > = 65 years | 3 Participants | 0 Participants | 14 Participants | 6 Participants | 23 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 71 Participants | 22 Participants | 102 Participants |
| Sex: Female, Male Male | 4 Participants | 3 Participants | 6 Participants | 11 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 8 | 4 / 8 | 39 / 77 | 21 / 33 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 77 | 0 / 33 |
Outcome results
Primary
American College of Rheumatology (ACR) 20% Responders at 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).
Time frame: Week 12
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc 300 mg BID (POC) | American College of Rheumatology (ACR) 20% Responders at Week 12 | 21 Participants |
| Placebo (POC) | American College of Rheumatology (ACR) 20% Responders at Week 12 | 6 Participants |
p-value: 0.15590% CI: [-6.16, 21.83]Barnard/Pearson chi-square test
Secondary
ACR 20% Responders at 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.
Time frame: Weeks 1, 2, 4, and 8
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 1 | 8 Participants |
| Maraviroc 300 mg BID (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 4 | 21 Participants |
| Maraviroc 300 mg BID (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 2 | 12 Participants |
| Maraviroc 300 mg BID (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 8 | 23 Participants |
| Placebo (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 2 | 5 Participants |
| Placebo (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 1 | 4 Participants |
| Placebo (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 8 | 7 Participants |
| Placebo (POC) | ACR 20% Responders at Weeks 1, 2, 4, and 8 | Week 4 | 8 Participants |
Comparison: Week 1p-value: 0.7990% CI: [-15.13, 8.68]Barnard/Pearson chi-square test
Comparison: Week 2p-value: 0.47790% CI: [-13.67, 11.64]Barnard/Pearson chi-square test
Comparison: Week 4p-value: 0.3790% CI: [-12.85, 16.77]Barnard/Pearson chi-square test
Comparison: Week 8p-value: 0.17590% CI: [-7.07, 22.03]Barnard/Pearson chi-square test
Secondary
ACR 50% Responders at 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.
Time frame: Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 2 | 2 Participants |
| Maraviroc 300 mg BID (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 8 | 6 Participants |
| Maraviroc 300 mg BID (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 4 | 2 Participants |
| Maraviroc 300 mg BID (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 12 | 8 Participants |
| Maraviroc 300 mg BID (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 1 | 1 Participants |
| Placebo (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 12 | 3 Participants |
| Placebo (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 1 | 0 Participants |
| Placebo (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 2 | 0 Participants |
| Placebo (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 4 | 2 Participants |
| Placebo (POC) | ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 | Week 8 | 3 Participants |
Comparison: Week 1p-value: 0.4290% CI: [-6.34, 6.01]Barnard/Pearson chi-square test
Comparison: Week 2p-value: 0.25890% CI: [-5.08, 7.95]Barnard/Pearson chi-square test
Comparison: Week 4p-value: 190% CI: [-14.39, 3.42]Barnard/Pearson chi-square test
Comparison: Week 8p-value: 0.89990% CI: [-13.56, 7.92]Barnard/Pearson chi-square test
Comparison: Week 12p-value: 0.48990% CI: [-11.24, 10.96]Barnard/Pearson chi-square test
Secondary
ACR 70% Responders at 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.
Time frame: Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 1 | 0 Participants |
| Maraviroc 300 mg BID (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 8 | 2 Participants |
| Maraviroc 300 mg BID (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 4 | 0 Participants |
| Maraviroc 300 mg BID (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 12 | 0 Participants |
| Maraviroc 300 mg BID (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 2 | 0 Participants |
| Placebo (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 12 | 1 Participants |
| Placebo (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 1 | 0 Participants |
| Placebo (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 2 | 0 Participants |
| Placebo (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 4 | 1 Participants |
| Placebo (POC) | ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 | Week 8 | 0 Participants |
Comparison: Week 4p-value: 190% CI: [-13.59, 1.28]Barnard/Pearson chi-square test
Comparison: Week 8p-value: 0.25890% CI: [-5.08, 7.95]Barnard/Pearson chi-square test
Comparison: Week 12p-value: 190% CI: [-13.59, 1.28]Barnard/Pearson chi-square test
Secondary
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
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)
Population: All available PK data from the Safety/PK Component were included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | 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 | Plasma MTX (Screening) | 909.4 ng.hr/mL | Standard Deviation 422.37 |
| Maraviroc 300 mg BID (POC) | 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 | Plasma MTX (Week 1) | 1045.6 ng.hr/mL | Standard Deviation 329.93 |
| Maraviroc 300 mg BID (POC) | 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 | Plasma Maraviroc (Week 1) | 451.6 ng.hr/mL | Standard Deviation 247.33 |
| Placebo (POC) | 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 | Plasma MTX (Screening) | 888.9 ng.hr/mL | Standard Deviation 249.51 |
| Placebo (POC) | 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 | Plasma MTX (Week 1) | 844.8 ng.hr/mL | Standard Deviation 273.92 |
| Placebo (POC) | 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 | Plasma Maraviroc (Week 1) | 1106.8 ng.hr/mL | Standard Deviation 1029.6 |
Secondary
Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate).
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
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). | 11.2 bpm | Standard Deviation 5.82 |
| Placebo (POC) | Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). | 8.8 bpm | Standard Deviation 5.76 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). | 12.0 bpm | Standard Deviation 6.4 |
| Placebo (POC) | Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). | 10.5 bpm | Standard Deviation 4.91 |
Secondary
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 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
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | 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]). | QTc Interval | 0 msec | Standard Deviation 0 |
| Maraviroc 300 mg BID (POC) | 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]). | QRS Complex | 7.6 msec | Standard Deviation 4.75 |
| Maraviroc 300 mg BID (POC) | 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]). | QTcF Interval | 22.9 msec | Standard Deviation 19.64 |
| Maraviroc 300 mg BID (POC) | 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]). | QT Interval | 35.0 msec | Standard Deviation 19.47 |
| Maraviroc 300 mg BID (POC) | 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]). | PR Interval | 19.7 msec | Standard Deviation 7.13 |
| Maraviroc 300 mg BID (POC) | 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]). | RR Interval | 137.0 msec | Standard Deviation 79.18 |
| Maraviroc 300 mg BID (POC) | 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]). | QTcB Interval | 23.1 msec | Standard Deviation 19.7 |
| Placebo (POC) | 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]). | QTc Interval | 0 msec | Standard Deviation 0 |
| Placebo (POC) | 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]). | RR Interval | 114.3 msec | Standard Deviation 63.38 |
| Placebo (POC) | 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]). | PR Interval | 13.0 msec | Standard Deviation 6.93 |
| Placebo (POC) | 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]). | QRS Complex | 7.3 msec | Standard Deviation 4.89 |
| Placebo (POC) | 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]). | QT Interval | 22.5 msec | Standard Deviation 10.67 |
| Placebo (POC) | 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]). | QTcB Interval | 23.3 msec | Standard Deviation 9.55 |
| Placebo (POC) | 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]). | QTcF Interval | 17.3 msec | Standard Deviation 7.16 |
| Maraviroc 300 mg BID (POC) | 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]). | QTcF Interval | 28.3 msec | Standard Deviation 18.77 |
| Maraviroc 300 mg BID (POC) | 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]). | QTc Interval | 19.6 msec | Standard Deviation 17.69 |
| Maraviroc 300 mg BID (POC) | 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]). | PR Interval | 16.2 msec | Standard Deviation 8 |
| Maraviroc 300 mg BID (POC) | 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]). | QTcB Interval | 27.9 msec | Standard Deviation 18.47 |
| Maraviroc 300 mg BID (POC) | 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]). | RR Interval | 140.0 msec | Standard Deviation 70.81 |
| Maraviroc 300 mg BID (POC) | 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]). | QRS Complex | 11.3 msec | Standard Deviation 6.56 |
| Maraviroc 300 mg BID (POC) | 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]). | QT Interval | 31.9 msec | Standard Deviation 18.74 |
| Placebo (POC) | 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]). | QRS Complex | 10.2 msec | Standard Deviation 5.35 |
| Placebo (POC) | 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]). | QT Interval | 28.7 msec | Standard Deviation 13.97 |
| Placebo (POC) | 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]). | PR Interval | 15.4 msec | Standard Deviation 10.47 |
| Placebo (POC) | 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]). | QTcB Interval | 30.2 msec | Standard Deviation 23.88 |
| Placebo (POC) | 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]). | QTc Interval | 20.3 msec | Standard Deviation 12.75 |
| Placebo (POC) | 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]). | RR Interval | 117.6 msec | Standard Deviation 48.26 |
| Placebo (POC) | 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]). | QTcF Interval | 29.8 msec | Standard Deviation 22.2 |
Secondary
Change From Baseline in CRP at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 2 | 3.14 mg/L | Standard Error 2.06 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 8 | 2.33 mg/L | Standard Error 2.1 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 4 | 3.36 mg/L | Standard Error 2.34 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 12 | 2.35 mg/L | Standard Error 2.26 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 1 | 1.20 mg/L | Standard Error 1.87 |
| Placebo (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 12 | 1.93 mg/L | Standard Error 3.22 |
| Placebo (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 1 | 3.40 mg/L | Standard Error 2.67 |
| Placebo (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 2 | 1.81 mg/L | Standard Error 2.93 |
| Placebo (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 4 | -1.30 mg/L | Standard Error 3.33 |
| Placebo (POC) | Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 | Week 8 | -1.14 mg/L | Standard Error 2.98 |
Comparison: Week 1p-value: 0.48190% CI: [-7.36, 2.96]ANCOVA
Comparison: Week 2p-value: 0.69890% CI: [-4.34, 6.99]ANCOVA
Comparison: Week 4p-value: 0.23390% CI: [-1.79, 11.1]ANCOVA
Comparison: Week 8p-value: 0.3290% CI: [-2.29, 9.25]ANCOVA
Comparison: Week 12p-value: 0.91290% CI: [-5.81, 6.64]ANCOVA
Secondary
Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.41 mg/L | Standard Error 0.12 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.82 mg/L | Standard Error 0.15 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.64 mg/L | Standard Error 0.14 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.73 mg/L | Standard Error 0.16 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.23 mg/L | Standard Error 0.09 |
| Placebo (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.63 mg/L | Standard Error 0.22 |
| Placebo (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.17 mg/L | Standard Error 0.13 |
| Placebo (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.33 mg/L | Standard Error 0.17 |
| Placebo (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.65 mg/L | Standard Error 0.19 |
| Placebo (POC) | Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.51 mg/L | Standard Error 0.21 |
Comparison: Week 1p-value: 0.65390% CI: [-0.31, 0.18]ANCOVA
Comparison: Week 2p-value: 0.70390% CI: [-0.41, 0.26]ANCOVA
Comparison: Week 4p-value: 0.96890% CI: [-0.37, 0.39]ANCOVA
Comparison: Week 8p-value: 0.2190% CI: [-0.72, 0.1]ANCOVA
Comparison: Week 12p-value: 0.69690% CI: [-0.53, 0.33]ANCOVA
Secondary
Change From Baseline in HAQ-DI at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.22 scores on scale | Standard Error 0.06 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.24 scores on scale | Standard Error 0.06 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.25 scores on scale | Standard Error 0.07 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.18 scores on scale | Standard Error 0.08 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.08 scores on scale | Standard Error 0.05 |
| Placebo (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.03 scores on scale | Standard Error 0.07 |
| Placebo (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.06 scores on scale | Standard Error 0.13 |
| Placebo (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.18 scores on scale | Standard Error 0.09 |
| Placebo (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.04 scores on scale | Standard Error 0.08 |
| Placebo (POC) | Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.03 scores on scale | Standard Error 0.1 |
Comparison: Week 1p-value: 0.46490% CI: [-0.19, 0.07]ANCOVA
Comparison: Week 2p-value: 0.06890% CI: [-0.35, -0.02]ANCOVA
Comparison: Week 4p-value: 0.53290% CI: [-0.23, 0.11]ANCOVA
Comparison: Week 8p-value: 0.06390% CI: [-0.41, -0.03]ANCOVA
Comparison: Week 12p-value: 0.39690% CI: [-0.36, 0.12]ANCOVA
Secondary
Change From Baseline in Mean Heart Rate
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
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Heart Rate | Standing Heart Rate | 14.6 beats per minute (bpm) | Standard Deviation 6.73 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Heart Rate | Supine Heart Rate | 15.0 beats per minute (bpm) | Standard Deviation 8.28 |
| Placebo (POC) | Change From Baseline in Mean Heart Rate | Supine Heart Rate | 10.4 beats per minute (bpm) | Standard Deviation 4.56 |
| Placebo (POC) | Change From Baseline in Mean Heart Rate | Standing Heart Rate | 8.1 beats per minute (bpm) | Standard Deviation 3.64 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Heart Rate | Standing Heart Rate | 11.8 beats per minute (bpm) | Standard Deviation 6.91 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Heart Rate | Supine Heart Rate | 11.6 beats per minute (bpm) | Standard Deviation 6.06 |
| Placebo (POC) | Change From Baseline in Mean Heart Rate | Standing Heart Rate | 11.4 beats per minute (bpm) | Standard Deviation 8.13 |
| Placebo (POC) | Change From Baseline in Mean Heart Rate | Supine Heart Rate | 9.2 beats per minute (bpm) | Standard Deviation 6.16 |
Secondary
Change From Baseline in Mean Orthostatic Blood Pressure (BP)
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
Population: FAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Diastolic BP | 10.3 mmHg | Standard Deviation 7.94 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Diastolic BP | 13.0 mmHg | Standard Deviation 4.97 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Systolic BP | 20.9 mmHg | Standard Deviation 13.18 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Systolic BP | 20.9 mmHg | Standard Deviation 13.58 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Diastolic BP | 8.3 mmHg | Standard Deviation 5.65 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Diastolic BP | 10.9 mmHg | Standard Deviation 5.08 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Systolic BP | 18.3 mmHg | Standard Deviation 9.51 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Systolic BP | 18.0 mmHg | Standard Deviation 7.71 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Systolic BP | 17.5 mmHg | Standard Deviation 13.86 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Systolic BP | 17.8 mmHg | Standard Deviation 11.25 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Diastolic BP | 12.2 mmHg | Standard Deviation 8.14 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Diastolic BP | 11.7 mmHg | Standard Deviation 6.98 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Diastolic BP | 10.8 mmHg | Standard Deviation 5.12 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Diastolic BP | 11.5 mmHg | Standard Deviation 5.15 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Supine Systolic BP | 18.0 mmHg | Standard Deviation 11.12 |
| Placebo (POC) | Change From Baseline in Mean Orthostatic Blood Pressure (BP) | Standing Systolic BP | 17.5 mmHg | Standard Deviation 12.36 |
Secondary
Change From Baseline in Patient's Assessment of Arthritis Pain at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -8.46 scores on scale | Standard Error 2.65 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -10.30 scores on scale | Standard Error 2.98 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -8.35 scores on scale | Standard Error 2.7 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -8.30 scores on scale | Standard Error 2.85 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -3.96 scores on scale | Standard Error 2.18 |
| Placebo (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -6.09 scores on scale | Standard Error 4.06 |
| Placebo (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -3.62 scores on scale | Standard Error 3.1 |
| Placebo (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -3.20 scores on scale | Standard Error 3.77 |
| Placebo (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -9.08 scores on scale | Standard Error 3.85 |
| Placebo (POC) | Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -8.67 scores on scale | Standard Error 4.24 |
Comparison: Week 1p-value: 0.92590% CI: [-6.41, 5.72]ANCOVA
Comparison: Week 2p-value: 0.23990% CI: [-12.62, 2.11]ANCOVA
Comparison: Week 4p-value: 0.87290% CI: [-6.79, 8.25]ANCOVA
Comparison: Week 8p-value: 0.74590% CI: [-9.91, 6.65]ANCOVA
Comparison: Week 12p-value: 0.64490% CI: [-10.14, 5.71]ANCOVA
Secondary
Change From Baseline in Patient's Global Assessment of Arthritis Pain at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -8.85 scores on scale | Standard Error 2.48 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -11.12 scores on scale | Standard Error 2.93 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -10.00 scores on scale | Standard Error 2.74 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -8.55 scores on scale | Standard Error 2.88 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -4.70 scores on scale | Standard Error 2.22 |
| Placebo (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -6.78 scores on scale | Standard Error 4.06 |
| Placebo (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -2.34 scores on scale | Standard Error 3.13 |
| Placebo (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -4.88 scores on scale | Standard Error 3.49 |
| Placebo (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -9.02 scores on scale | Standard Error 3.86 |
| Placebo (POC) | Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -3.44 scores on scale | Standard Error 4.13 |
Comparison: Week 1p-value: 0.52490% CI: [-8.49, 3.77]ANCOVA
Comparison: Week 2p-value: 0.33890% CI: [-10.8, 2.87]ANCOVA
Comparison: Week 4p-value: 0.8390% CI: [-8.55, 6.58]ANCOVA
Comparison: Week 8p-value: 0.11890% CI: [-15.76, 0.4]ANCOVA
Comparison: Week 12p-value: 0.71290% CI: [-9.73, 6.18]ANCOVA
Secondary
Change From Baseline in Physician's Global Assessment of Arthritis Pain at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.44 scores on scale | Standard Error 0.09 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.63 scores on scale | Standard Error 0.1 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.49 scores on scale | Standard Error 0.1 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.49 scores on scale | Standard Error 0.11 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.30 scores on scale | Standard Error 0.08 |
| Placebo (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 12 | -0.36 scores on scale | Standard Error 0.15 |
| Placebo (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.22 scores on scale | Standard Error 0.11 |
| Placebo (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 2 | -0.39 scores on scale | Standard Error 0.12 |
| Placebo (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 4 | -0.44 scores on scale | Standard Error 0.13 |
| Placebo (POC) | Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 | Week 8 | -0.37 scores on scale | Standard Error 0.14 |
Comparison: Week 1p-value: 0.5490% CI: [-0.28, 0.13]ANCOVA
Comparison: Week 2p-value: 0.75790% CI: [-0.28, 0.19]ANCOVA
Comparison: Week 4p-value: 0.76790% CI: [-0.31, 0.21]ANCOVA
Comparison: Week 8p-value: 0.11290% CI: [-0.52, 0.01]ANCOVA
Comparison: Week 12p-value: 0.4990% CI: [-0.42, 0.17]ANCOVA
Secondary
Change From Baseline in SF-36 Mental Component Summary at 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.
Time frame: Baseline, Weeks 4 and 12
Population: FAS
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 | Week 12 | 1.17 scores on a scale | Standard Error 1.41 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 | Week 4 | 1.42 scores on a scale | Standard Error 1.25 |
| Placebo (POC) | Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 | Week 12 | 0.61 scores on a scale | Standard Error 2.25 |
| Placebo (POC) | Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 | Week 4 | 0.72 scores on a scale | Standard Error 1.75 |
Comparison: Week 4p-value: 0.73490% CI: [-2.71, 4.11]ANCOVA
Comparison: Week 12p-value: 0.81890% CI: [-3.5, 4.62]ANCOVA
Secondary
Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at 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.
Time frame: Baseline, Weeks 4 and 12
Population: FAS
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 | Week 4 | 4.33 scores on a scale | Standard Error 0.89 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 | Week 12 | 3.14 scores on a scale | Standard Error 1.04 |
| Placebo (POC) | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 | Week 4 | 3.76 scores on a scale | Standard Error 1.25 |
| Placebo (POC) | Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 | Week 12 | 4.81 scores on a scale | Standard Error 1.65 |
Comparison: Week 4p-value: 0.69890% CI: [-1.87, 3.01]ANCOVA
Comparison: Week 12p-value: 0.34490% CI: [-4.62, 1.26]ANCOVA
Secondary
Change From Baseline in Swollen Joint Count at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 1 | -1.39 joint count | Standard Error 0.49 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 4 | -3.93 joint count | Standard Error 0.54 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 2 | -2.25 joint count | Standard Error 0.61 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 8 | -4.48 joint count | Standard Error 0.62 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 12 | -3.48 joint count | Standard Error 0.66 |
| Placebo (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 8 | -3.03 joint count | Standard Error 0.88 |
| Placebo (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 12 | -3.43 joint count | Standard Error 0.95 |
| Placebo (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 1 | -1.07 joint count | Standard Error 0.7 |
| Placebo (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 2 | -2.51 joint count | Standard Error 0.87 |
| Placebo (POC) | Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 4 | -4.08 joint count | Standard Error 0.77 |
Comparison: Week 1p-value: 0.790% CI: [-1.7, 1.06]ANCOVA
Comparison: Week 2p-value: 0.79990% CI: [-1.45, 1.97]ANCOVA
Comparison: Week 4p-value: 0.86790% CI: [-1.35, 1.66]ANCOVA
Comparison: Week 8p-value: 0.16790% CI: [-3.17, 0.28]ANCOVA
Comparison: Week 12p-value: 0.96690% CI: [-1.91, 1.81]ANCOVA
Secondary
Change From Baseline in Tender/Painful Joint Count at 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.
Time frame: Baseline, Weeks 1, 2, 4, 8, and 12
Population: FAS. Missing values were imputed by the method of LOCF.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 2 | -2.08 joint count | Standard Error 0.76 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 8 | -4.85 joint count | Standard Error 0.85 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 4 | -4.00 joint count | Standard Error 0.84 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 12 | -4.89 joint count | Standard Error 0.84 |
| Maraviroc 300 mg BID (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 1 | -0.81 joint count | Standard Error 0.68 |
| Placebo (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 12 | -3.41 joint count | Standard Error 1.19 |
| Placebo (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 1 | -1.91 joint count | Standard Error 0.96 |
| Placebo (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 2 | -2.38 joint count | Standard Error 1.08 |
| Placebo (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 4 | -4.01 joint count | Standard Error 1.2 |
| Placebo (POC) | Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 | Week 8 | -3.24 joint count | Standard Error 1.21 |
Comparison: Week 1p-value: 0.33590% CI: [-0.79, 2.99]ANCOVA
Comparison: Week 2p-value: 0.81690% CI: [-1.82, 2.41]ANCOVA
Comparison: Week 4p-value: 0.99690% CI: [-2.35, 2.36]ANCOVA
Comparison: Week 8p-value: 0.26390% CI: [-3.98, 0.76]ANCOVA
Comparison: Week 12p-value: 0.29490% CI: [-3.82, 0.85]ANCOVA
Secondary
Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1
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)
Population: All available PK data from the Safety/PK Component were included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Screening) | 338.7 ng/mL | Standard Deviation 143.94 |
| Maraviroc 300 mg BID (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Week 1) | 403.8 ng/mL | Standard Deviation 97.46 |
| Maraviroc 300 mg BID (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma Maraviroc (Week 1) | 199.59 ng/mL | Standard Deviation 115.603 |
| Placebo (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Screening) | 352.1 ng/mL | Standard Deviation 115.72 |
| Placebo (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Week 1) | 322.8 ng/mL | Standard Deviation 104.2 |
| Placebo (POC) | Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma Maraviroc (Week 1) | 461.03 ng/mL | Standard Deviation 365.715 |
Secondary
Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 480 to < 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 480 to < 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 450 to < 480 msec | 1 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 450 to < 480 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 480 to < 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 450 to < 480 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval > = 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 450 to < 480 msec | 3 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 450 to < 480 msec | 2 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 480 to < 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval > = 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 450 to < 480 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval > = 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 480 to < 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 480 to < 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 480 to < 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 480 to < 500 msec | 2 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 450 to < 480 msec | 9 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 450 to < 480 msec | 13 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 450 to < 480 msec | 2 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval > = 500 msec | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 480 to < 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval > = 500 msec | 1 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 450 to < 480 msec | 2 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 480 to < 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval 450 to < 480 msec | 5 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcF Interval > = 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval > = 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTc Interval 480 to < 500 msec | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 450 to < 480 msec | 8 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline | Maximum QTcB Interval 480 to < 500 msec | 1 Participants |
Secondary
Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Systolic BP | 1 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Diastolic BP | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Diastolic BP | 1 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Systolic BP | 2 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Diastolic BP | 1 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Systolic BP | 1 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Systolic BP | 1 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Diastolic BP | 0 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Systolic BP | 2 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Diastolic BP | 8 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Systolic BP | 4 Participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Diastolic BP | 3 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Systolic BP | 3 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Diastolic BP | 2 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Supine Diastolic BP | 0 Participants |
| Placebo (POC) | Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline | Maximum Increase in Standing Systolic BP | 2 Participants |
Secondary
Number of Subjects With Withdrawal From Study Due to Lack of Efficacy
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Number of Subjects With Withdrawal From Study Due to Lack of Efficacy | Overall Withdrawal | 22 participants |
| Maraviroc 300 mg BID (POC) | Number of Subjects With Withdrawal From Study Due to Lack of Efficacy | Withdrawal due to Lack of Efficacy | 5 participants |
| Placebo (POC) | Number of Subjects With Withdrawal From Study Due to Lack of Efficacy | Overall Withdrawal | 14 participants |
| Placebo (POC) | Number of Subjects With Withdrawal From Study Due to Lack of Efficacy | Withdrawal due to Lack of Efficacy | 2 participants |
p-value: 0.649Fisher Exact
Secondary
Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy.
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
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 1 (n=77, 33) | 1.00 proportion |
| Maraviroc 300 mg BID (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 2 (n=77, 32) | 1.00 proportion |
| Maraviroc 300 mg BID (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 4 (n=76, 32) | 1.00 proportion |
| Maraviroc 300 mg BID (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 8 (n=69, 31) | 0.99 proportion |
| Maraviroc 300 mg BID (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 12 (n=58, 21) | 0.93 proportion |
| Placebo (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 12 (n=58, 21) | 0.92 proportion |
| Placebo (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 8 (n=69, 31) | 1.00 proportion |
| Placebo (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 2 (n=77, 32) | 1.00 proportion |
| Placebo (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 1 (n=77, 33) | 1.00 proportion |
| Placebo (POC) | Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. | Week 4 (n=76, 32) | 1.00 proportion |
p-value: 0.9826Log Rank
Secondary
Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1
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)
Population: All available PK data from the Safety/PK Component were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc 300 mg BID (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Week 1) | 1.000 hr |
| Maraviroc 300 mg BID (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma Maraviroc (Week 1) | 2.000 hr |
| Maraviroc 300 mg BID (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Screening) | 2.000 hr |
| Placebo (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Screening) | 1.000 hr |
| Placebo (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma MTX (Week 1) | 1.500 hr |
| Placebo (POC) | Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 | Plasma Maraviroc (Week 1) | 2.500 hr |