Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00413660
First received: December 18, 2006
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to determine the effectiveness and safety, over 6 months, of 6 dose regimens of CP-690,550, combined with methotrexate, for the treatment of adults with active rheumatoid arthritis.


Condition Intervention Phase
Arthritis, Rheumatoid
Drug: CP-690,550
Other: placebo
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 2B, Randomized, Double Blind, Placebo-Controlled, Multicenter Study To Compare 6 Dose Regimens Of CP-690,550 Vs. Placebo, Each Combined With Methotrexate, Administered For 6 Months In The Treatment Of Subjects With Active Rheumatoid Arthritis Who Have Had An Inadequate Response To 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: >= 20% improvement in tender joints count (TJC); >= 20% improvement in swollen joints 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 2, 4, 6, 8, 16, 20, 24/Early Termination (ET) ] [ 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 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    ACR50 response: >= 50% improvement in TJC or SJC 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 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    ACR70 response: >= 70% improvement in TJC or SJC 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.

  • Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve [ Time Frame: Baseline up to Week 2, 4, 6, 8, 12 ] [ 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. The area under the curve (AUC) for ACR-n is the measure of the area under the curve of the mean change from baseline in ACR-n. The trapezoidal rule was used to compute the AUC.

  • Tender Joints Count (TJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 Joints Count (TJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 Joints Count (SJC) [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 Joints Count (SJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 mm = no pain and 100 mm = most severe pain.

  • Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    Participants rated the severity of arthritis pain on a 0 to 100 mm VAS, where 0 mm = no pain and 100 mm = most severe pain.

  • Patient Global Assessment (PtGA) of Arthritis [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 mm = very well and 100 mm = very poorly.

  • Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 mm = very well and 100 mm = very poorly.

  • Physician Global Assessment of Arthritis [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

  • Change From Baseline in Physician Global Assessment of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.

  • Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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. Change = scores at observation minus score at Baseline, and total possible score ranged from -3 to 3. A negative value in change from baseline indicates an improvement.

  • C-Reactive Protein (CRP) [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 deciliter (mg/dL) to 10 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Change From Baseline in C-Reactive Protein (CRP) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ 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 ultra-sensitive assay. Normal range of CRP is 0 mg/dL to 10 mg/dL. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints 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 and more than (>) 3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) less than (<) 2.6 = remission.

  • Change From Baseline in Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET [ Time Frame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    DAS28-3 (CRP) was calculated from the SJC and TJC using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) <= 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission.

  • Percentage of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP) [ Time Frame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    Disease improvement was classified as good, moderate, and none based on improvement in DAS 28-3 (CRP) from baseline and present DAS 28-3 (CRP) score. Good: an improvement from baseline of >1.2 and a present score of <=3.2; none: an improvement of <=0.6 or >0.6 to <=1.2 with a present score of >5.1; remaining participants were classified as having moderate (Mod) improvement. Scores of good and moderate were considered to have therapeutic response.

  • Percentage of Participants With Disease Remission Based on DAS28-3 (CRP) [ Time Frame: Week 2, 4, 6, 8, 12, 16, 20, 24/ET ] [ Designated as safety issue: No ]
    DAS28-3 (CRP) defined remission was classified as a score of <2.6.

  • 36-Item Short-Form Health Survey (SF-36) [ Time Frame: Baseline, Week 12, 24/ET ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). The score for a section is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning).

  • Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ET ] [ Designated as safety issue: No ]
    SF-36 is a standardized survey evaluating 8 domains (of 2 components [C]; physical [Ph] and mental [Mn]) of functional health and well being: physical and social (So) functioning (Fn), physical and emotional role (role-physical [R-P], role-emotional [R-E]) limitations, bodily pain (BP), general health (GH), vitality (Vit), mental health (MnH). 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-5 Dimentions (EQ-5D) - Health State Profile Utility Score [ Time Frame: Baseline, Week 12, 24/ET ] [ 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 From Baseline in Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility at Week 12 and 24/ET [ Time Frame: Baseline, Week 12, 24/ET ] [ 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.

  • Medical Outcome Study- Sleep Scale (MOS-SS) [ Time Frame: Baseline, Week 2, 12, 24/ET ] [ Designated as safety issue: No ]
    Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range:0-100); sleep quantity (Qua)(range:0-24), and optimal (Opt) sleep (yes: 1, no: 0)and nine item index measures of sleep disturbance were constructed to provide composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range* 100); total score range: 0 to 100; higher score = greater intensity of attribute.

  • Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ET ] [ Designated as safety issue: No ]
    Participant-rated questionnaire to assess key constructs of sleep over the past week. Consists of a 12-item based on 7 subscales: sleep disturbance (SD), snoring (Sno), awakened short of breath (ASOB) or with headache, sleep adequacy (Ade), and somnolence (Som) (range: 0-100); sleep quantity (Qua) (range: 0-24), and optimal (Opt) sleep (yes: 1, no: 0) and 9 item index measures of sleep disturbance were constructed to provide 2 composite scores: sleep problem summary (SPS) and overall sleep problems (OSP). Except sleep adequacy, optimal sleep and quantity, higher scores=greater impairment. Scores are transformed (actual raw score minus lowest possible score divided by possible raw score range*100); total score range: 0 to 100; higher score = greater intensity of attribute.

  • Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale [ Time Frame: Baseline, Week 2, 12, 24/ET ] [ Designated as safety issue: No ]
    FACIT-Fatigue scale (FS) 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-FS 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.

  • Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET [ Time Frame: Baseline, Week 2, 12, 24/ET ] [ Designated as safety issue: No ]
    FACIT-FS 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-FS 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: 509
Study Start Date: January 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CP 690,550 1 mg BID Drug: CP-690,550
4 blinded tablets administered BID
Experimental: CP 690,550 10 mg BID Drug: CP-690,550
4 blinded tablets administered BID
Experimental: CP 690,550 15 mg Drug: CP-690,550
4 blinded tablets administered BID
Experimental: CP 690,550 3 mg BID Drug: CP-690,550
4 blinded tablets administered BID
Experimental: CP 690,550 5 mg BID Drug: CP-690,550
4 blinded tablets administered BID
Experimental: CP-690,550 20 mg QD Drug: CP-690,550
Oral tablets
Placebo Comparator: Placebo
Dummy tablets
Other: placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years and older
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: NCT00413660

  Show 82 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00413660     History of Changes
Other Study ID Numbers: A3921025
Study First Received: December 18, 2006
Results First Received: December 4, 2012
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
DMARD therapy

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 September 16, 2014