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Comparison Of 4 CP-690,550 Doses Vs. Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis in Japan

Phase 2
Completed
Conditions
Arthritis, Rheumatoid
Interventions
Drug: Placebo
Drug: CP-690,550
Registration Number
NCT00603512
Lead Sponsor
Pfizer
Brief Summary

The purpose of this study is to determine the effectiveness and safety, over 3 months, of 4 dose regimens of CP-690,550, combined with methotrexate, for the treatment with active rheumatoid arthritis.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
140
Inclusion Criteria
  • Active rheumatoid arthritis
  • Inadequate response to stably dosed methotrexate
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Exclusion Criteria
  • Current therapy with any DMARD or biologic other than methotrexate
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
CP-690,550, 0mgPlacebo-
CP-690,550, 10mgCP-690,550-
CP-690,550, 3mgCP-690,550-
CP-690,550, 5mgCP-690,550-
CP-690,550, 1mgCP-690,550-
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12Week 12

ACR20 response: greater than or equal to (\>=) 20 percent (%) improvement in tender joint count (TJC); \>= 20% improvement in swollen joint count (SJC); 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).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) ResponseWeek 1, 2, 4, 8

ACR20 response: \>= 20% improvement in TJC; \>= 20% improvement in SJC; 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 HAQ); and CRP.

Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) ResponseWeek 1, 2, 4, 8, 12/End of Treatment (EOT)

ACR50 response: \>= 50% improvement in tender or swollen joint counts 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 HAQ); and CRP.

Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) ResponseWeek 1, 2, 4, 8, 12/EOT

ACR70 response: \>= 70% improvement in tender or swollen joint counts 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 HAQ); and CRP.

Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) ResponseWeek 1, 2, 4, 8, 12/EOT

ACR90 response: \>= 90% improvement in tender or swollen joint counts 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 HAQ); and CRP.

Tender Joint Count (TJC)Baseline, Week 1, 2, 4, 8, 12/EOT

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.

Change From Baseline in Tender Joint Count (TJC) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

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.

Swollen Joint Count (SJC)Baseline, Week 1, 2, 4, 8, 12/EOT

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.

Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

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.

Patient Assessment of Arthritis PainBaseline, Week 1, 2, 4, 8, 12/EOT

Participants rated the severity of arthritis pain on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), where 0 = no pain and 100 = most severe pain.

Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 = no pain and 100 = most severe pain.

Patient Global Assessment (PtGA) of ArthritisBaseline, Week 1, 2, 4, 8, 12/EOT

Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 = very well and 100 = very poorly.

Change From Baseline in Patient Global Assessment of Arthritis (PtGA) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

Participants answered: "Considering all the ways your arthritis affects you, how are you feeling today?" Participants responded by using a 0 - 100 mm VAS, where 0 = very well and 100 = very poorly.

Physician Global Assessment (PGA) of ArthritisBaseline, Week 1, 2, 4, 8, 12/EOT

Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.

Change From Baseline in Physician Global Assessment of Arthritis (PGA) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.

Health Assessment Questionnaire-Disability Index (HAQ-DI)Baseline, Week 1, 2, 4, 8, 12/EOT

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 From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

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.

C-Reactive Protein (CRP)Baseline, Week 1, 2, 4, 8, 12/EOT

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 milligram per liter (mg/L) to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 12/EOTBaseline, Week 1, 2, 4, 8, 12/EOT

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. Normal range of CRP is 0 milligram per liter (mg/L) to 10 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

Numeric Index of American College of Rheumatology Response (ACR-n)Week 1, 2, 4, 8, 12/EOT

ACR-n = calculated for each participant by taking the lowest percentage improvement in (1) SJC or (2) TJC or (3) the median of the remaining 5 components of the 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.

Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) CurveBaseline up to Week 12

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.

Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])Baseline, Week 1, 2, 4, 8, 12/EOT

DAS28-3 (CRP) was calculated from SJC and TJC using 28 joint count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (=\<) 3.2 implied low disease activity, \>3.2 to 5.1 implied moderate to high disease activity and \<2.6 implied remission.

Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])Baseline, Week 1, 2, 4, 8, 12/EOT

DAS28-4 (ESR) calculated from SJC and TJC using 28 joint count, erythrocyte sedimentation rate (ESR) (millimeters per hour \[mm/hour\]) and patient's global assessment (PtGA) of disease activity (transformed score ranging 0 to 10; higher score indicated greater affectation due to disease activity). Total score range:0 to 9.4, higher score indicated 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 and less than (\<) 2.6=remission.

36-Item Short-Form Health Survey (SF-36)Baseline, Week 12/EOT

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).

Euro Quality of Life (EQ-5D)- Health State Profile Utility ScoreBaseline, Week 12/EOT

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, selfcare, 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.

Medical Outcome Study- Sleep Scale (MOS-SS)Baseline, Week 2, 12/EOT

Participant-rated 12 item questionnaire assess constructs of sleep over past week.7 subscales:sleep disturbance(SD),snoring(Sno),awakened short of breath(ASOB),sleep adequacy(Ade),somnolence(Som)(range:0-100);sleep quantity(Qua)(range:0-24),optimal(Opt) sleep(yes:1,no:0),9 item index measures of sleep disturbance provide composite scores:sleep problem summary(SPS),overall SP(OSP).Except Ade,Opt,Qua,higher scores=more impairment.Scores transformed(actual raw score(RS) minus lowest possible score divided by possible RS range\*100);total score range:0-100;higher score=more intensity of attribute.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue ScaleBaseline, Week 2, 12/EOT

FACIT-F is a 13-item questionnaire. Participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions (with the exception of 2 negatively stated), the greater the fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as 4 minus the participant's response. The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflected an improvement in the participant's health status.

Trial Locations

Locations (1)

Pfizer Investigational Site

🇯🇵

Niigata, Japan

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