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
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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 ]

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 ]

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 ]
  Hide Outcome Measure 43

Measure Type Secondary
Measure Title Work Limitations Questionnaire (WLQ) Score at Month 6
Measure Description WLQ: participant-reported 25-item scale to evaluate degree to which health problems interfere with an ability to perform job roles along 4 dimensions: Time Management scale (TMS)(5-items); Physical Demands scale (PDS) (6-item); Mental-Interpersonal Demands Scale (MIDS) (9-items); Output Demands Scale (ODS) (5-items). All the scales ranged from 0 (limited none of the time) to 100 (limited all of the time). Work Loss Index (WLI), which represented percentage of lost work over time period relative to a normative population, was derived (total score: 0 [no loss] to 100 [complete loss of work]).
Time Frame Month 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.

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]
  40     45     24     19  
Work Limitations Questionnaire (WLQ) Score at Month 6  
[units: units on a scale]
Mean ± Standard Deviation
       
Month 6: TMS (n=39,42,23,18)     26.96  ± 29.72     30.77  ± 27.83     32.50  ± 30.79     32.73  ± 25.10  
Month 6: PDS (n=38,42,24,18)     47.53  ± 36.97     44.65  ± 30.60     40.94  ± 27.82     47.15  ± 29.47  
Month 6: MIDS (n=40,45,24,19)     18.50  ± 26.90     29.84  ± 29.03     31.95  ± 32.26     30.68  ± 32.09  
Month 6: ODS (n=39,44,24,19)     21.32  ± 27.74     29.20  ± 29.00     30.50  ± 31.94     33.68  ± 28.02  
Month 6: WLI (n=40,45,24,19)     6.87  ± 6.53     8.78  ± 7.07     9.27  ± 7.06     9.62  ± 7.41  

No statistical analysis provided for Work Limitations Questionnaire (WLQ) Score at 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
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Time Frame No text entered.
Additional Description The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   2%  

Reporting Groups
  Description
CP-690,550 5 mg Up to Month 3 CP-690,550 5 mg tablet orally twice daily up to Month 3.
CP-690,550 10 mg Up to Month 3 CP-690,550 10 mg tablets orally twice daily up to Month 3.
Placebo Up to Month 3 Placebo matching to CP-690,550 5 mg tablet orally twice daily up to Month 3.
CP-690,550 5 mg From Month 3 to 6 CP-690,550 5 mg tablet orally twice daily from Month 3 to Month 6.
CP-690,550 10 mg From Month 3 to 6 CP-690,550 10 mg tablets orally twice daily from Month 3 to Month 6.

Other Adverse Events
    CP-690,550 5 mg Up to Month 3     CP-690,550 10 mg Up to Month 3     Placebo Up to Month 3     CP-690,550 5 mg From Month 3 to 6     CP-690,550 10 mg From Month 3 to 6  
Total, other (not including serious) adverse events            
# participants affected / at risk     37/133     43/134     46/132     35/199     30/200  
Gastrointestinal disorders            
Abdominal pain upper * 1          
# participants affected / at risk     3/133 (2.26%)     1/134 (0.75%)     0/132 (0.00%)     0/199 (0.00%)     0/200 (0.00%)  
Constipation * 1          
# participants affected / at risk     4/133 (3.01%)     3/134 (2.24%)     1/132 (0.76%)     0/199 (0.00%)     0/200 (0.00%)  
Diarrhoea * 1          
# participants affected / at risk     8/133 (6.02%)     5/134 (3.73%)     5/132 (3.79%)     0/199 (0.00%)     0/200 (0.00%)  
Mouth ulceration * 1          
# participants affected / at risk     0/133 (0.00%)     0/134 (0.00%)     0/132 (0.00%)     4/199 (2.01%)     0/200 (0.00%)  
Nausea * 1          
# participants affected / at risk     4/133 (3.01%)     2/134 (1.49%)     9/132 (6.82%)     4/199 (2.01%)     1/200 (0.50%)  
General disorders            
Fatigue * 1          
# participants affected / at risk     1/133 (0.75%)     3/134 (2.24%)     0/132 (0.00%)     0/199 (0.00%)     0/200 (0.00%)  
Oedema peripheral * 1          
# participants affected / at risk     3/133 (2.26%)     1/134 (0.75%)     5/132 (3.79%)     0/199 (0.00%)     0/200 (0.00%)  
Infections and infestations            
Bronchitis * 1          
# participants affected / at risk     0/133 (0.00%)     0/134 (0.00%)     0/132 (0.00%)     6/199 (3.02%)     3/200 (1.50%)  
Nasopharyngitis * 1          
# participants affected / at risk     5/133 (3.76%)     6/134 (4.48%)     4/132 (3.03%)     6/199 (3.02%)     5/200 (2.50%)  
Sinusitis * 1          
# participants affected / at risk     1/133 (0.75%)     1/134 (0.75%)     4/132 (3.03%)     1/199 (0.50%)     4/200 (2.00%)  
Upper respiratory tract infection * 1          
# participants affected / at risk     5/133 (3.76%)     2/134 (1.49%)     4/132 (3.03%)     5/199 (2.51%)     8/200 (4.00%)  
Urinary tract infection * 1          
# participants affected / at risk     5/133 (3.76%)     3/134 (2.24%)     3/132 (2.27%)     4/199 (2.01%)     2/200 (1.00%)  
Injury, poisoning and procedural complications            
Muscle strain * 1          
# participants affected / at risk     0/133 (0.00%)     3/134 (2.24%)     0/132 (0.00%)     0/199 (0.00%)     0/200 (0.00%)  
Investigations            
Blood creatine phosphokinase increased * 1          
# participants affected / at risk     0/133 (0.00%)     3/134 (2.24%)     0/132 (0.00%)     0/199 (0.00%)     0/200 (0.00%)  
Musculoskeletal and connective tissue disorders            
Arthralgia * 1          
# participants affected / at risk     1/133 (0.75%)     1/134 (0.75%)     5/132 (3.79%)     0/199 (0.00%)     0/200 (0.00%)  
Back pain * 1          
# participants affected / at risk     2/133 (1.50%)     3/134 (2.24%)     2/132 (1.52%)     2/199 (1.01%)     4/200 (2.00%)  
Muscle spasms * 1          
# participants affected / at risk     0/133 (0.00%)     1/134 (0.75%)     3/132 (2.27%)     0/199 (0.00%)     0/200 (0.00%)  
Rheumatoid arthritis * 1          
# participants affected / at risk     3/133 (2.26%)     1/134 (0.75%)     4/132 (3.03%)     7/199 (3.52%)     0/200 (0.00%)  
Nervous system disorders            
Headache * 1          
# participants affected / at risk     3/133 (2.26%)     8/134 (5.97%)     1/132 (0.76%)     1/199 (0.50%)     4/200 (2.00%)  
Paraesthesia * 1          
# participants affected / at risk     0/133 (0.00%)     1/134 (0.75%)     3/132 (2.27%)     0/199 (0.00%)     0/200 (0.00%)  
Psychiatric disorders            
Depression * 1          
# participants affected / at risk     2/133 (1.50%)     4/134 (2.99%)     1/132 (0.76%)     0/199 (0.00%)     0/200 (0.00%)  
Renal and urinary disorders            
Haematuria * 1          
# participants affected / at risk     0/133 (0.00%)     0/134 (0.00%)     3/132 (2.27%)     0/199 (0.00%)     0/200 (0.00%)  
Respiratory, thoracic and mediastinal disorders            
Cough * 1          
# participants affected / at risk     3/133 (2.26%)     0/134 (0.00%)     5/132 (3.79%)     0/199 (0.00%)     0/200 (0.00%)  
Skin and subcutaneous tissue disorders            
Skin lesion * 1          
# participants affected / at risk     1/133 (0.75%)     3/134 (2.24%)     0/132 (0.00%)     0/199 (0.00%)     0/200 (0.00%)  
Vascular disorders            
Hypertension * 1          
# participants affected / at risk     1/133 (0.75%)     3/134 (2.24%)     1/132 (0.76%)     4/199 (2.01%)     2/200 (1.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA 13.1



  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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