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

December 18, 2006
January 14, 2013
January 2007
August 2008   (final data collection date for primary outcome measure)
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).
American College of Rheumatology 20 (ACR20) response rates at week 12
Complete list of historical versions of study NCT00413660 on ClinicalTrials.gov Archive Site
  • 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.
ACR 20, 50 and 70 response rates; DAS 28-3(CRP) and quality of life assessments at multiple timepoints
Not Provided
Not Provided
 
Comparison Of 6 CP-690,550 Doses Vs.Placebo, Each Combined With Methotrexate, For The Treatment Of Rheumatoid Arthritis
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

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.

Not Provided
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Arthritis, Rheumatoid
  • Drug: CP-690,550
    4 blinded tablets administered BID
  • Drug: CP-690,550
    Oral tablets
  • Other: placebo
    Placebo
  • Experimental: CP 690,550 1 mg BID
    Intervention: Drug: CP-690,550
  • Experimental: CP 690,550 10 mg BID
    Intervention: Drug: CP-690,550
  • Experimental: CP 690,550 15 mg
    Intervention: Drug: CP-690,550
  • Experimental: CP 690,550 3 mg BID
    Intervention: Drug: CP-690,550
  • Experimental: CP 690,550 5 mg BID
    Intervention: Drug: CP-690,550
  • Experimental: CP-690,550 20 mg QD
    Intervention: Drug: CP-690,550
  • Placebo Comparator: Placebo
    Dummy tablets
    Intervention: Other: placebo
Kremer JM, Cohen S, Wilkinson BE, Connell CA, French JL, Gomez-Reino J, Gruben D, Kanik KS, Krishnaswami S, Pascual-Ramos V, Wallenstein G, Zwillich SH. A phase IIb dose-ranging study of the oral JAK inhibitor tofacitinib (CP-690,550) versus placebo in combination with background methotrexate in patients with active rheumatoid arthritis and an inadequate response to methotrexate alone. Arthritis Rheum. 2012 Apr;64(4):970-81. doi: 10.1002/art.33419. Epub 2011 Oct 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
509
August 2008
August 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Active rheumatoid arthritis
  • Inadequate response to stably dosed methotrexate

Exclusion Criteria:

  • Current therapy with any DMARD or biologic other than methotrexate
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Brazil,   Bulgaria,   Chile,   Czech Republic,   Hungary,   Mexico,   Poland,   Slovakia,   Spain,   Sweden,   Turkey
 
NCT00413660
A3921025
No
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP