Maraviroc in Rheumatoid Arthritis

This study has been terminated.
(See Detailed Description.)
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00427934
First received: January 25, 2007
Last updated: November 10, 2010
Last verified: November 2010
Results First Received: October 6, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: Maraviroc
Drug: Maraviroc Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Maraviroc 150 mg BID (Pharmacokinetic [PK]) 150 mg tablet was administered by mouth twice a day (BID) for 4 weeks with stable weekly doses of methotrexate (MTX).
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.
Maraviroc 300 mg BID (Proof-of-Concept [POC]) 300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Placebo (POC) Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.

Participant Flow:   Overall Study
    Maraviroc 150 mg BID (Pharmacokinetic [PK])     Maraviroc 300 mg BID (PK)     Maraviroc 300 mg BID (Proof-of-Concept [POC])     Placebo (POC)  
STARTED     8     8     78     34  
Treated     8     8     77     33  
COMPLETED     7     8     55     19  
NOT COMPLETED     1     0     23     15  
Adverse Event                 1                 0                 5                 4  
Lack of Efficacy                 0                 0                 5                 2  
Randomized But Did Not Receive Treatment                 0                 0                 1                 1  
Unknown                 0                 0                 11                 5  
Withdrawal by Subject                 0                 0                 1                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Maraviroc 150 mg BID (PK) 150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.
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.
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.
Placebo (POC) Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Total Total of all reporting groups

Baseline Measures
    Maraviroc 150 mg BID (PK)     Maraviroc 300 mg BID (PK)     Maraviroc 300 mg BID (POC)     Placebo (POC)     Total  
Number of Participants  
[units: participants]
  8     8     77     33     126  
Age, Customized  
[units: Participants]
         
< 18 years     0     0     0     0     0  
18 to 44 years     1     0     15     6     22  
45 to 64 years     4     8     48     21     81  
> = 65 years     3     0     14     6     23  
Gender  
[units: Participants]
         
Female     4     5     71     22     102  
Male     4     3     6     11     24  



  Outcome Measures
  Show All Outcome Measures

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

2.  Secondary:   ACR 20% Responders at Weeks 1, 2, 4, and 8   [ Time Frame: Weeks 1, 2, 4, and 8 ]

3.  Secondary:   ACR 50% Responders at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Weeks 1, 2, 4, 8, and 12 ]

4.  Secondary:   ACR 70% Responders at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Weeks 1, 2, 4, 8, and 12 ]

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

6.  Secondary:   Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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

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

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

10.  Secondary:   Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

11.  Secondary:   Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

12.  Secondary:   Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12   [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]
  Hide Outcome Measure 12

Measure Type Secondary
Measure Title Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Measure 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  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS. Missing values were imputed by the method of LOCF.

Reporting Groups
  Description
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.
Placebo (POC) Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.

Measured Values
    Maraviroc 300 mg BID (POC)     Placebo (POC)  
Number of Participants Analyzed  
[units: participants]
  72     31  
Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12  
[units: mg/L]
Least Squares Mean ± Standard Error
   
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 for Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.653
Mean Difference (Final Values) [4] -0.07
90% Confidence Interval ( -0.31 to 0.18 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 1
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.703
Mean Difference (Final Values) [4] -0.08
90% Confidence Interval ( -0.41 to 0.26 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 2
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.968
Mean Difference (Final Values) [4] 0.01
90% Confidence Interval ( -0.37 to 0.39 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 4
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.210
Mean Difference (Final Values) [4] -0.31
90% Confidence Interval ( -0.72 to 0.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 8
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 5 for Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12
Groups [1] All groups
Method [2] ANCOVA
P Value [3] 0.696
Mean Difference (Final Values) [4] -0.10
90% Confidence Interval ( -0.53 to 0.33 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Week 12
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  This analysis was carried out using ANCOVA with baseline DAS28-4 (CRP) as the covariate, treatment, country as fixed effects.
[4] Other relevant estimation information:
  No text entered.



13.  Secondary:   Change From Baseline in Mean Orthostatic Blood Pressure (BP)   [ Time Frame: Baseline, 16 weeks ]

14.  Secondary:   Change From Baseline in Mean Heart Rate   [ Time Frame: Baseline, 16 weeks ]

15.  Secondary:   Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline   [ Time Frame: Baseline, 16 weeks ]

16.  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]).   [ Time Frame: Baseline, 16 weeks ]

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

18.  Secondary:   Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline   [ Time Frame: Baseline, 16 weeks ]

19.  Secondary:   Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12   [ Time Frame: Baseline, Weeks 4 and 12 ]

20.  Secondary:   Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12   [ Time Frame: Baseline, Weeks 4 and 12 ]

21.  Secondary:   Number of Subjects With Withdrawal From Study Due to Lack of Efficacy   [ Time Frame: 16 weeks ]

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

23.  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   [ Time Frame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose) ]

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

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


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer
ClinicalTrials.gov Identifier: NCT00427934     History of Changes
Other Study ID Numbers: A4001056
Study First Received: January 25, 2007
Results First Received: October 6, 2009
Last Updated: November 10, 2010
Health Authority: United States: Food and Drug Administration