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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00687193
First received: May 22, 2008
Last updated: March 19, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: Placebo
Drug: CP-690,550
Phase 2

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
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 (5 Doses) Or Placebo In Subjects With Active Rheumatoid Arthritis Inadequately Responding To At Least 1 DMARD

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    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).


Secondary Outcome Measures:
  • Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Weeks 2, 4 and 8 [ Time Frame: Week 2, 4, and 8 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving American College of Rheumatology 50% (ACR50) Response [ Time Frame: Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving American College of Rheumatology 70% (ACR70) Response [ Time Frame: Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Achieving American College of Rheumatology 90% (ACR90) Response [ Time Frame: Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Disease Activity Score Based on 28-Joints Count Using C-reactive Protein [DAS28-3(CRP)] [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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


  • Change From Baseline in Disease Activity Score Based on 28-Joints Count Using Erythrocyte Sedimentation Rate [DAS28-4(ESR)] [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Painful and Tender Joint Counts [ Time Frame: Baseline, Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Swollen Joint Count (SJC) [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Patient's Assessment of Pain [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in Patient's Global Assessment of Arthritis [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Physician's Global Assessment of Arthritis [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in C- Reactive Protein (CRP) (mg/L) [ Time Frame: Baseline, Week 2, 4, 8 and 12 ] [ Designated as safety issue: No ]
    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.

  • Area Under Curve (AUC) for Change From Baseline in American College of Rheumatology-N (ACR-N) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Euro Quality of Life (EQ-5D) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Physical Functioning Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Physical Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Bodily Pain Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -General Health Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Vitality Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Social Functioning Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Role-Emotional Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) -Mental Health Domain [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Physical Component Summary (PCS) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.


  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) - Mental Component Summary (MCS) [ Time Frame: Baseline, Week 12 ] [ Designated as safety issue: No ]

    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.



Enrollment: 318
Study Start Date: March 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Placebo BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 10mg Drug: CP-690,550
10mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 15mg Drug: CP-690,550
15mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 1mg Drug: CP-690,550
1mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 3mg Drug: CP-690,550
3mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 5mg Drug: CP-690,550
5mg BID, 3 blinded tablets administered BID for 12 weeks

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00687193

Locations
Japan
Pfizer Investigational Site
Nagoya, Aichi, Japan
Pfizer Investigational Site
Narashino, Chiba, Japan
Pfizer Investigational Site
Yotukaidou, Chiba, Japan
Pfizer Investigational Site
Iiduka, Fukuoka, Japan
Pfizer Investigational Site
Kitakyusyu, Fukuoka, Japan
Pfizer Investigational Site
Kurume, Fukuoka, Japan
Pfizer Investigational Site
Sawara-ku, Fukuoka, Japan
Pfizer Investigational Site
Takasaki, Gunma, Japan
Pfizer Investigational Site
Higashihiroshima, Hiroshima, Japan
Pfizer Investigational Site
Hiroshima-city, Hiroshima, Japan
Pfizer Investigational Site
Asahikawa, Hokkaido, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
Pfizer Investigational Site
Nishinomiya, Hyogo, Japan
Pfizer Investigational Site
Tsukuba, Ibaraki, Japan
Pfizer Investigational Site
Sagamihara, Kanagawa, Japan
Pfizer Investigational Site
Koushi, Kumamoto, Japan
Pfizer Investigational Site
Tsu, Mie, Japan
Pfizer Investigational Site
Sendai, Miyagi, Japan
Pfizer Investigational Site
Ohmura, Nagasaki, Japan
Pfizer Investigational Site
Sasebo, Nagasaki, Japan
Pfizer Investigational Site
Kashihara, Nara, Japan
Pfizer Investigational Site
Kawachinagano, Osaka, Japan
Pfizer Investigational Site
Ureshino-shi, Saga, Japan
Pfizer Investigational Site
Kawagoe-shi, Saitama, Japan
Pfizer Investigational Site
Kitamoto, Saitama, Japan
Pfizer Investigational Site
Arakawa-ku, Tokyo, Japan
Pfizer Investigational Site
Bunkyo-ku, Tokyo, Japan
Pfizer Investigational Site
Musashimurayama-shi, Tokyo, Japan
Pfizer Investigational Site
Setagaya-ku, Tokyo, Japan
Pfizer Investigational Site
Shinjyuku-ku, Tokyo, Japan
Pfizer Investigational Site
Takaoka, Toyama, Japan
Pfizer Investigational Site
Chiba, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Fukusima, Japan
Pfizer Investigational Site
Hiroshima, Japan
Pfizer Investigational Site
Kumamoto, Japan
Pfizer Investigational Site
Kyoto, Japan
Pfizer Investigational Site
Nagasaki, Japan
Pfizer Investigational Site
Oita, Japan
Pfizer Investigational Site
Osaka, Japan
Pfizer Investigational Site
Saitama, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00687193     History of Changes
Other Study ID Numbers: A3921040
Study First Received: May 22, 2008
Results First Received: November 26, 2012
Last Updated: March 19, 2013
Health Authority: Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Pfizer:
Phase 2 monotherapy in Japan

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Tofacitinib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014