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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00603512
First received: January 17, 2008
Last updated: December 16, 2012
Last verified: December 2012
  Purpose

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.


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 (4 Doses) or Placebo in Subjects With Active Rheumatoid Arthritis Inadequately Controlled With Methotrexate Alone

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Percentage of Participants Achieving 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 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:
  • Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response [ Time Frame: Week 1, 2, 4, 8 ] [ Designated as safety issue: No ]
    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) Response [ Time Frame: Week 1, 2, 4, 8, 12/End of Treatment (EOT) ] [ Designated as safety issue: No ]
    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) Response [ Time Frame: Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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) Response [ Time Frame: Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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.

  • Change From Baseline in Tender Joint Count (TJC) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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.

  • Swollen Joint Count (SJC) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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.

  • Change From Baseline in Swollen Joint Count (SJC) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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.

  • Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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 Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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 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/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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 VAS, where 0 = very well and 100 = very poorly.

  • Physician Global Assessment (PGA) of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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 From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 1, 2, 4, 8 and 12/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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.

  • C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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. 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/EOT [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ 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. 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) [ Time Frame: Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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) Curve [ Time Frame: Baseline up to 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.

  • Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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]) [ Time Frame: Baseline, Week 1, 2, 4, 8, 12/EOT ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline, Week 12/EOT ] [ 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).

  • Euro Quality of Life (EQ-5D)- Health State Profile Utility Score [ Time Frame: Baseline, Week 12/EOT ] [ 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, 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) [ Time Frame: Baseline, Week 2, 12/EOT ] [ Designated as safety issue: No ]
    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 Scale [ Time Frame: Baseline, Week 2, 12/EOT ] [ Designated as safety issue: No ]
    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.


Enrollment: 140
Study Start Date: January 2008
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: CP-690,550, 0mg Drug: Placebo
0 mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 10mg Drug: CP-690,550
10 mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 1mg Drug: CP-690,550
1 mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 3mg Drug: CP-690,550
3 mg BID, 3 blinded tablets administered BID for 12 weeks
Experimental: CP-690,550, 5mg Drug: CP-690,550
5 mg 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:

  • Active rheumatoid arthritis
  • Inadequate response to stably dosed methotrexate

Exclusion Criteria:

  • Current therapy with any DMARD or biologic other than methotrexate
  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: NCT00603512

Locations
Japan
Pfizer Investigational Site
Hitachi-shi, Ibaraki, Japan
Pfizer Investigational Site
Sagamihara, Kanagawa, Japan
Pfizer Investigational Site
Yahatanishi-ku, Kitakyusyu, Japan
Pfizer Investigational Site
Koushi, Kumamoto, Japan
Pfizer Investigational Site
Sendai, Miyagi, Japan
Pfizer Investigational Site
Kawachinagano, Osaka, Japan
Pfizer Investigational Site
Kawagoe-shi, Saitama, Japan
Pfizer Investigational Site
Kitamoto, Saitama, Japan
Pfizer Investigational Site
Bunkyo-k, Tokyo, Japan
Pfizer Investigational Site
Bunkyo-ku, Tokyo, Japan
Pfizer Investigational Site
Chiyoda-ku, Tokyo, Japan
Pfizer Investigational Site
Koto-ku, Tokyo, Japan
Pfizer Investigational Site
Meguro-ku, Tokyo, Japan
Pfizer Investigational Site
Musashimurayama-shi, Tokyo, Japan
Pfizer Investigational Site
Shinjyuku-ku, Tokyo, Japan
Pfizer Investigational Site
Chiba, Japan
Pfizer Investigational Site
Fukuoka, Japan
Pfizer Investigational Site
Niigata, 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: NCT00603512     History of Changes
Other Study ID Numbers: A3921039
Study First Received: January 17, 2008
Results First Received: November 14, 2012
Last Updated: December 16, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Pfizer:
Phase II MTX add-on study in Japan

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Tofacitinib
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on July 31, 2014