Three Dose Levels of CP-690,550 Monotherapy Versus Placebo, Administered Orally Twice Daily (BID) for 6 Weeks

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00147498
First received: September 2, 2005
Last updated: December 20, 2012
Last verified: December 2012
  Purpose

The study's objective is to compare the efficacy of 3 dose levels of oral CP-690,550 monotherapy (5 mg, 15 mg, and 30 mg twice daily [BID]) versus placebo administered over 6 weeks for the treatment of the signs and symptoms of subjects with active rheumatoid arthritis (RA).


Condition Intervention Phase
Rheumatoid Arthritis
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 2a, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study To Compare 3 Dose Levels Of CP-690,550 Versus Placebo, Administered Orally Twice Daily (BID) For 6 Weeks, In The Treatment Of The Signs And Symptoms Of Subjects With Active Rheumatoid Arthritis

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 6 [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
    ACR20 response: greater than or equal to (>=) 20 percent (%) 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 1, 2, 4, and 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, 6, and 8 ] [ 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 1, 2, 4, 6, and 8 ] [ 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 6 ] [ Designated as safety issue: No ]
    ACR-n: calculated 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 AUC 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 1, 2, 4, 6, and 8 ] [ 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 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 indicated an improvement.

  • Swollen Joints Count (SJC) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 Global Assessment (PtGA) of Arthritis [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 millimeter (mm) Visual Analog Scale (VAS) where 0 mm = very well and 100 mm = very poorly.

  • Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 1, 2, 4, 6, and 8 ] [ 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 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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.

  • Patient Assessment of Arthritis Pain [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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.

  • Change From Baseline in Patient Assessment of Arthritis Pain at Week 1, 2, 4, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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.

  • Health Assessment Questionnaire-Disability Index (HAQ-DI) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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, 6, and 8 ] [ 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 100 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, 6 and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 mg/L to 100 mg/L. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Disease Activity Score Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity and greater than (>) 3.2 to 5.1 implied moderate to high disease activity, and less than (<) 2.6 = remission.

  • Change From Baseline in Disease Activity Score Using 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) at Week 1, 2, 4, 6, and 8 [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ 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 ranging 0 to 9.4; higher scores indicated greater affectation due to disease activity. DAS 28-3 (CRP) <=3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and <2.6 = remission.

  • Number of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP) [ Time Frame: Baseline, Week 1, 2, 4, 6, and 8 ] [ Designated as safety issue: No ]
    Disease improvement was classified as good, moderate, and no change 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 improvement. Scores of good and moderate were considered to have therapeutic response.


Enrollment: 264
Study Start Date: January 2005
Study Completion Date: June 2006
Primary Completion Date: June 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5 mg BID
CP 690,550 5 mg BID
Drug: CP-690,550
Oral tablets administered at a dose of 5 mg BID for 6 weeks
Experimental: 15 mg BID
CP 690,550 15 mg BID
Drug: CP-690,550
Oral tablets administered at a dose of 15 mg BID for 6 weeks
Experimental: 30 mg BID
Oral tablets administered at a dose of 30 mg BID for 6 weeks
Drug: CP-690,550
30 mg BID for 6 weeks
Placebo Comparator: Placebo
Placebo
Other: Placebo
Placebo tablets

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • The subject has a history of inadequate response to at least 1, but no more than 4, of the following DMARDs: sulfasalazine, injectable gold, methotrexate, leflunomide, cyclosporine, or a thiopurine derivative (azathioprine or 6-mercaptopurine)

Exclusion Criteria:

  • Current Therapy With Any DMARD Or Biologic
  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: NCT00147498

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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: NCT00147498     History of Changes
Other Study ID Numbers: A3921019
Study First Received: September 2, 2005
Results First Received: November 19, 2012
Last Updated: December 20, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
oral JAK inhibitor
clinical trial
joint diseases
anti-Inflammatory agents
rheumatic diseases
DMARD
Antirheumatic Agents
Autoimmune Diseases
Immune System Diseases

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

ClinicalTrials.gov processed this record on October 21, 2014