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

Arthritis, Rheumatoid Clinical Trial

Official title:

A Phase 2, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Confirm Dose Responsiveness Following 12 Weeks of the Administration of CP-690,550 (4 Doses) or Placebo in Subjects With Active Rheumatoid Arthritis Inadequately Controlled With Methotrexate Alone

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00603512
• Other study ID #: A3921039
• Status: Completed
• Phase: Phase 2
• First received: January 17, 2008
• Last updated: December 16, 2012
• Start date: January 2008
• Est. completion date: September 2008

Study information

• Verified date: December 2012
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: Japan: Ministry of Health, Labor and Welfare
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: September 2008
• Est. primary completion date: September 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 70 Years

Eligibility

Inclusion Criteria:

• Active rheumatoid arthritis

• Inadequate response to stably dosed methotrexate

Exclusion Criteria:

• Current therapy with any DMARD or biologic other than methotrexate

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• Placebo
0 mg BID, 3 blinded tablets administered BID for 12 weeks
• CP-690,550
10 mg BID, 3 blinded tablets administered BID for 12 weeks
• CP-690,550
1 mg BID, 3 blinded tablets administered BID for 12 weeks
• CP-690,550
3 mg BID, 3 blinded tablets administered BID for 12 weeks
• CP-690,550
5 mg BID, 3 blinded tablets administered BID for 12 weeks

Locations

Country	Name	City	State
Japan	Pfizer Investigational Site	Bunkyo-k	Tokyo
Japan	Pfizer Investigational Site	Bunkyo-ku	Tokyo
Japan	Pfizer Investigational Site	Chiba
Japan	Pfizer Investigational Site	Chiyoda-ku	Tokyo
Japan	Pfizer Investigational Site	Fukuoka
Japan	Pfizer Investigational Site	Hitachi-shi	Ibaraki
Japan	Pfizer Investigational Site	Kawachinagano	Osaka
Japan	Pfizer Investigational Site	Kawagoe-shi	Saitama
Japan	Pfizer Investigational Site	Kitamoto	Saitama
Japan	Pfizer Investigational Site	Koto-ku	Tokyo
Japan	Pfizer Investigational Site	Koushi	Kumamoto
Japan	Pfizer Investigational Site	Meguro-ku	Tokyo
Japan	Pfizer Investigational Site	Musashimurayama-shi	Tokyo
Japan	Pfizer Investigational Site	Niigata
Japan	Pfizer Investigational Site	Sagamihara	Kanagawa
Japan	Pfizer Investigational Site	Sendai	Miyagi
Japan	Pfizer Investigational Site	Shinjyuku-ku	Tokyo
Japan	Pfizer Investigational Site	Yahatanishi-ku	Kitakyusyu

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 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).	Week 12	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	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.	Week 1, 2, 4, 8	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	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.	Week 1, 2, 4, 8, 12/End of Treatment (EOT)	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	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.	Week 1, 2, 4, 8, 12/EOT	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 90% (ACR90) Response	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.	Week 1, 2, 4, 8, 12/EOT	No
Secondary	Tender Joint Count (TJC)	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Tender Joint Count (TJC) at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Patient Assessment of Arthritis Pain	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Patient Global Assessment (PtGA) 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 VAS, where 0 = very well and 100 = very poorly.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Patient Global Assessment of Arthritis (PtGA) at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Physician Global Assessment (PGA) of Arthritis	Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Physician Global Assessment of Arthritis (PGA) at Week 1, 2, 4, 8 and 12/EOT	Physician Global Assessment of Arthritis was measured on a 0 to 100 mm VAS, where 0 = very good and 100 = very bad.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	C-Reactive Protein (CRP)	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Change From Baseline in C-Reactive Protein (CRP) at Week 1, 2, 4, 8 and 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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Numeric Index of American College of Rheumatology Response (ACR-n)	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.	Week 1, 2, 4, 8, 12/EOT	No
Secondary	Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve	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 up to Week 12	No
Secondary	Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	Disease Activity Score Using 28-Joint Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 [ESR])	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.	Baseline, Week 1, 2, 4, 8, 12/EOT	No
Secondary	36-Item Short-Form Health Survey (SF-36)	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).	Baseline, Week 12/EOT	No
Secondary	Euro Quality of Life (EQ-5D)- Health State Profile Utility Score	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.	Baseline, Week 12/EOT	No
Secondary	Medical Outcome Study- Sleep Scale (MOS-SS)	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.	Baseline, Week 2, 12/EOT	No
Secondary	Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale	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.	Baseline, Week 2, 12/EOT	No

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