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Study of CP-690,550 Versus Placebo In Rheumatoid Arthritis Patients On Background Methotrexate With Inadequate Response To Tumor Necrosis Factor (TNF) Inhibitors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00960440
First received: August 14, 2009
Last updated: December 6, 2012
Last verified: December 2012
Results First Received: December 6, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Arthritis, Rheumatoid
Interventions: Drug: CP-690,550
Drug: 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
CP-690,550 5 mg CP-690,550 5 milligram (mg) tablet orally twice daily up to Month 6.
CP-690,550 10 mg CP-690,550 10 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 5 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 5 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 10 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 10 mg tablet twice daily orally up to Month 6.

Participant Flow:   Overall Study
    CP-690,550 5 mg     CP-690,550 10 mg     Placebo, Then CP-690,550 5 mg     Placebo, Then CP-690,550 10 mg  
STARTED     133     134     66     66  
COMPLETED     107     103     53     48  
NOT COMPLETED     26     31     13     18  
Death                 0                 0                 0                 1  
Adverse Event                 12                 12                 4                 4  
Lack of Efficacy                 2                 5                 3                 8  
Protocol Violation                 2                 8                 3                 4  
Withdrawal by Subject                 9                 5                 2                 1  
Unspecified                 1                 1                 1                 0  



  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
CP-690,550 5 mg CP-690,550 5 mg tablet orally twice daily up to Month 6.
CP-690,550 10 mg CP-690,550 10 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 5 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 5 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 10 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 10 mg tablet twice daily orally up to Month 6.
Total Total of all reporting groups

Baseline Measures
    CP-690,550 5 mg     CP-690,550 10 mg     Placebo, Then CP-690,550 5 mg     Placebo, Then CP-690,550 10 mg     Total  
Number of Participants  
[units: participants]
  133     134     66     66     399  
Age  
[units: years]
Mean ± Standard Deviation
  55.4  ± 11.5     55.1  ± 11.3     54.3  ± 11.7     54.5  ± 11.0     55.0  ± 11.3  
Gender  
[units: participants]
         
Female     113     116     53     53     335  
Male     20     18     13     13     64  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 3   [ Time Frame: Month 3 ]

2.  Primary:   Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Month 3   [ Time Frame: Baseline, Month 3 ]

3.  Primary:   Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3   [ Time Frame: Month 3 ]
  Hide Outcome Measure 3

Measure Type Primary
Measure Title Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3
Measure Description DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, erythrocyte sedimentation rate (ESR)(millimeter/hour [mm/hour]) and patient's global assessment (PtGA) of disease activity (participant rated arthritis activity assessment). Total score range:0-9.4, higher score=more disease activity. DAS28-4 (ESR) less than or equal to (<=)3.2 implied low disease activity, greater than (>)3.2 to 5.1 implied moderate to high disease activity, less than (<)2.6=remission. For comparison of CP-690,550 with placebo, placebo sequences were combined into single reporting group for Month 3 analysis.
Time Frame Month 3  
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 included all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline measurement. Missing values due to participant dropping due to any reason were imputed using NRI. Here 'N' (Number of Participants Analyzed) signifies participants who were evaluable for this measure.

Reporting Groups
  Description
CP-690,550 5 mg CP-690,550 5 mg tablet orally twice daily up to Month 6.
CP-690,550 10 mg CP-690,550 10 mg tablet orally twice daily up to Month 6.
Placebo Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 5mg or 10 mg tablet orally twice daily up to Month 6.

Measured Values
    CP-690,550 5 mg     CP-690,550 10 mg     Placebo  
Number of Participants Analyzed  
[units: participants]
  119     125     120  
Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3  
[units: percentage of participants]
  6.72     11.20     1.67  


Statistical Analysis 1 for Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3
Groups [1] CP-690,550 10 mg vs. Placebo
Method [2] Normal Approximation
P Value [3] 0.0017
Percentage Difference [4] 9.53
Standard Error of the mean ± 3.05
95% Confidence Interval ( 3.54 to 15.51 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Normal approximation for the difference in binomial proportions was used to test the superiority of CP-690,550 10 mg to placebo and 2-sided 95% CI was evaluated for the difference in percentages.
[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:
  A step-down procedure was used to control for multiple comparisons. For the comparison of 10 mg to placebo to be statistically significant in this measure, the comparison of 10 mg to placebo in HAQ-DI had to be statistically significant.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Percentage of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 at Month 3
Groups [1] CP-690,550 5 mg vs. Placebo
Method [2] Normal Approximation
P Value [3] 0.0496
Percentage Difference [4] 5.05
Standard Error of the mean ± 2.57
95% Confidence Interval ( 0.00 to 10.10 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Normal approximation for the difference in binomial proportions was used to test the superiority of CP-690,550 5 mg to placebo and 2-sided 95% CI was evaluated for the difference in percentages.
[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:
  Step-down procedure: For the comparison of 5 mg to placebo to be statistically significant in this measure, the comparison of 10 mg to placebo as well as comparison of 5 mg to placebo in HAQ-DI had to be statistically significant.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 2 and Month 1   [ Time Frame: Week 2, Month 1 ]

5.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

6.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 2, Month 1 and 3   [ Time Frame: Week 2, Month 1, 3 ]

7.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Month 4.5 and 6   [ Time Frame: Month 4.5 and 6 ]

8.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Week 2, Month 1 and 3   [ Time Frame: Week 2, Month 1, 3 ]

9.  Secondary:   Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

10.  Secondary:   Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

11.  Secondary:   Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

12.  Secondary:   Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

13.  Secondary:   Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) at Month 6   [ Time Frame: Month 6 ]

14.  Secondary:   Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, Month 1 and 3   [ Time Frame: Week 2, Month 1, 3 ]

15.  Secondary:   Health Assessment Questionnaire-Disability Index (HAQ-DI) at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

16.  Secondary:   Patient Assessment of Arthritis Pain at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

17.  Secondary:   Patient Assessment of Arthritis Pain at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]
  Hide Outcome Measure 17

Measure Type Secondary
Measure Title Patient Assessment of Arthritis Pain at Month 4.5 and 6
Measure Description Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.
Time Frame Month 4.5, 6  
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 included all randomized participants who received at least 1 dose of study treatment and had at least 1 post-baseline measurement. Here 'N' (Number of Participants Analyzed) signifies participants who were evaluable for this measure and ‘n’ signifies participants who were evaluable at specified time points for each arm group, respectively.

Reporting Groups
  Description
CP-690,550 5 mg CP-690,550 5 mg tablet orally twice daily up to Month 6.
CP-690,550 10 mg CP-690,550 10 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 5 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 5 mg tablet orally twice daily up to Month 6.
Placebo, Then CP-690,550 10 mg Placebo matched to CP-690,550 tablet orally twice daily up to Month 3 followed by CP-690,550 10 mg tablet twice daily orally up to Month 6.

Measured Values
    CP-690,550 5 mg     CP-690,550 10 mg     Placebo, Then CP-690,550 5 mg     Placebo, Then CP-690,550 10 mg  
Number of Participants Analyzed  
[units: participants]
  112     115     56     53  
Patient Assessment of Arthritis Pain at Month 4.5 and 6  
[units: units on a scale]
Mean ± Standard Deviation
       
Month 4.5 (n=112,115,56,53)     38.93  ± 26.40     35.01  ± 24.60     33.11  ± 23.44     40.62  ± 26.67  
Month 6 (n=104,103,51,49)     34.38  ± 25.33     29.56  ± 22.77     31.37  ± 24.76     40.71  ± 25.88  

No statistical analysis provided for Patient Assessment of Arthritis Pain at Month 4.5 and 6



18.  Secondary:   Patient Global Assessment (PtGA) of Arthritis Pain at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

19.  Secondary:   Patient Global Assessment (PtGA) of Arthritis Pain at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

20.  Secondary:   Physician Global Assessment of Arthritis at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

21.  Secondary:   Physician Global Assessment of Arthritis at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

22.  Secondary:   36-Item Short-Form Health Survey (SF-36) at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

23.  Secondary:   36-Item Short-Form Health Survey (SF-36) at Month 6   [ Time Frame: Month 6 ]

24.  Secondary:   Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1 and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

25.  Secondary:   Medical Outcomes Study Sleep Scale (MOS-SS) at Month 6   [ Time Frame: Month 6 ]

26.  Secondary:   Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Baseline, Week 2, Month 1, and 3   [ Time Frame: Baseline, Week 2, Month 1, 3 ]

27.  Secondary:   Number of Participants With Optimal Sleep Assessed Using Medical Outcomes Study Sleep Scale (MOS-SS) at Month 6   [ Time Frame: Month 6 ]

28.  Secondary:   Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

29.  Secondary:   Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Month 6   [ Time Frame: Month 6 ]

30.  Secondary:   Euro Quality of Life - 5 Dimensions (EQ-5D)- Health State Profile Utility Score at Baseline, Month 1 and 3   [ Time Frame: Baseline, Month 1, 3 ]

31.  Secondary:   Euro Quality of Life - 5 Dimensions (EQ-5D) - Health State Profile Utility Score at Month 6   [ Time Frame: Month 6 ]

32.  Secondary:   Work Productivity and Healthcare Resource Utilization (HCRU) at Baseline, Month 3   [ Time Frame: Baseline, Month 3 ]

33.  Secondary:   Work Productivity and Healthcare Resource Utilization (HCRU) at Month 6   [ Time Frame: Month 6 ]

34.  Secondary:   Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

35.  Secondary:   Number of Events Including Visits, Surgeries, Tests or Devices as Assessed Using RA-HCRU at Month 6   [ Time Frame: Month 6 ]

36.  Secondary:   Number of Days as Assessed Using RA-HCRU at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

37.  Secondary:   Number of Days as Assessed Using RA-HCRU at Month 6   [ Time Frame: Month 6 ]

38.  Secondary:   Number of Hours Per Day as Assessed RA-HCRU at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

39.  Secondary:   Number of Hours Per Day as Assessed RA-HCRU at Month 6   [ Time Frame: Month 6 ]

40.  Secondary:   Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

41.  Secondary:   Work Performance in Past 3 Months on Days Bothered as Assessed Using RA-HCRU at Month 6   [ Time Frame: Month 6 ]

42.  Secondary:   Work Limitations Questionnaire (WLQ) Score at Baseline and Month 3   [ Time Frame: Baseline, Month 3 ]

43.  Secondary:   Work Limitations Questionnaire (WLQ) Score at Month 6   [ Time Frame: Month 6 ]

44.  Other Pre-specified:   Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Week 2, Month 1 and 3   [ Time Frame: Week 2, Month 1, 3 ]

45.  Other Pre-specified:   Number of Participants With Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 4.5 and 6   [ Time Frame: Month 4.5, 6 ]

46.  Other Pre-specified:   Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 3   [ Time Frame: Month 3 ]

47.  Other Pre-specified:   Number of Participants With Disease Activity Score Based on 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR]) Less Than 2.6 and Less Than or Equal to 3.2 at Month 6   [ Time Frame: Month 6 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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