Comparison Of 5 CP-690,550 Doses Vs. Placebo, For The Treatment Of Rheumatoid Arthritis In Japan

Study Overview
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Brief Summary
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To evaluate the dose-response relationship of 5 dose of CP-690,550, compared to placebo for the treatment of signs and symptoms in patients with active RA who failed an adequate trial of therapy with at least 1 DMARD in a 12-week therapy.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Confirm Dose Responsiveness Following 12 Weeks Of The Administration Of CP-690,550 (5 Doses) Or Placebo In Subjects With Active Rheumatoid Arthritis Inadequately Responding To At Least 1 DMARD

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: Placebo
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550
* Drug: CP-690,550


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have failed an adequate trial of therapy with at least 1 DMARD due to lack of efficacy or toxicity. Exclusion Criteria: Current therapy with any DMARD

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo BID, 3 blinded tablets administered BID for 12 weeks<br>|
| Experimental: CP-690,550, 10mg<br> | Drug: CP-690,550<br>* 10mg BID, 3 blinded tablets administered BID for 12 weeks<br>|
| Experimental: CP-690,550, 15mg<br> | Drug: CP-690,550<br>* 15mg BID, 3 blinded tablets administered BID for 12 weeks<br>|
| Experimental: CP-690,550, 1mg<br> | Drug: CP-690,550<br>* 1mg BID, 3 blinded tablets administered BID for 12 weeks<br>|
| Experimental: CP-690,550, 3mg<br> | Drug: CP-690,550<br>* 3mg BID, 3 blinded tablets administered BID for 12 weeks<br>|
| Experimental: CP-690,550, 5mg<br> | Drug: CP-690,550<br>* 5mg BID, 3 blinded tablets administered BID for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 | ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in painful and tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4 and 8 | ACR20 response: greater than or equal to (>=) 20 percent (%) improvement in painful and tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP)at each visit. | Week 2, 4, and 8 | 
| Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response | ACR50 response: greater than or equal to (>=) 50 percent (%) improvement in painful and tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP) at each visit. | Week 2, 4, 8 and 12 | 
| Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response | ACR70 response: greater than or equal to (>=) 70 percent (%) improvement in painful and tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP) at each visit. | Week 2, 4, 8 and 12 | 
| Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response | ACR90 response: greater than or equal to (>=) 90 percent (%) improvement in painful and tender joint count; >= 90% improvement in swollen joint count; and >= 90% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP) at each visit. | Week 2, 4, 8 and 12 | 
| Change From Baseline in Disease Activity Score Based on 28-Joints Count Using C-reactive Protein [DAS28-3(CRP)] | The DAS28-3 (CRP) score is a measure of the perticipant's disease activity. It is based on the painful and tender joint count (28 joints), swollen joint count (28 joints) and CRP. DAS28-3 (CRP) scores range from 0 - 10; higher scores indicated greater affectation due to disease activity. Change = value at observation minus value at baseline | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Disease Activity Score Based on 28-Joints Count Using Erythrocyte Sedimentation Rate [DAS28-4(ESR)] | The DAS28-4 (ESR) score is a measure of the participant's disease activity. It is based on the painful and tender joint count (28 joints), swollen joint count (28 joints), participant's global assessment of disease activity (mm), and ESR. DAS28-4(ESR) scores range from 0 - 10; higher scores indicated greater affectation due to disease activity. Change = score at observation minus score at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) | HAQ-DI: participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty. Change = score at observation minus score at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Painful and Tender Joint Counts | Number of tender joints was determined by examining 68 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline. | Baseline, Weeks 2, 4, 8 and 12 | 
| Change From Baseline in Swollen Joint Count (SJC) | Number of swollen joints was determined by examination of 66 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Patient's Assessment of Pain | Change from Baseline in Patient's Assessment of Arthritis Pain -VAS (0 to 100 mm visual analog scale, 0 being no pain and 100 being most severe pain) was computed as Week 2, 4, 8 or 12 values minus baseline value. A negative value in change from baseline indicates an improvement. Change = value at observation minus value at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Patient's Global Assessment of Arthritis | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 - 100 mm Visual Analog Scale where 0 = very well and 100 = very poorly. Change = score at observation minus score at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in Physician's Global Assessment of Arthritis | Physician Global Assessment of Disease Activity was measured on a 0 to 100 mm Visual Analog Scale (VAS), with 0 mm = no disease activity; very good and 100 mm = worst disease activity; very poor. Change = score at observation minus score at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Change From Baseline in C- Reactive Protein (CRP) (mg/L) | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. Change = value at observation minus value at baseline. | Baseline, Week 2, 4, 8 and 12 | 
| Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N) | ACR-N = calculated for each participant by taking lowest percentage improvement in (1) swollen joint count or (2) tender joint count or (3) the median of remaining 5 components of ACR response (participant's assessment of disease activity; participant's global assessment of pain; physician's assessment of disease activity; participant's assessment of physical function; an acute phase reactant value - CRP). Negative numbers indicate worsening. The AUC for ACR-N is measure of the area under the curve of the mean change from baseline in ACR-N. The trapezoidal rule was used to compute AUC. | Baseline, Week 12 | 
| Change From Baseline in Euro Quality of Life (EQ-5D) | EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state. Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Physical Functioning Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Physical Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Bodily Pain Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -General Health Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Vitality Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change =score at Week 12 minus score at baseline | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Social Functioning Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Emotional Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Mental Health Domain | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Physical Component Summary (PCS) | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 
| Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Mental Component Summary (MCS) | SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). Change = score at Week 12 minus score at baseline. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 2 monotherapy in Japan