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

• ClinicalTrials.gov Identifier: NCT00687193
• Recruitment Status: Completed
• First Posted: May 30, 2008
• Results First Posted: December 25, 2012
• Last Update Posted: March 25, 2013
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 22, 2008
• First Posted Date: May 30, 2008
• Results First Submitted Date: November 26, 2012
• Results First Posted Date: December 25, 2012
• Last Update Posted Date: March 25, 2013
• Study Start Date: March 2009
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2012)

Number of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12 [ Time Frame: Week 12 ]

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).

• Original Primary Outcome Measures (submitted: May 23, 2008): ACR 20 responder rate at Week 12 [ Time Frame: At week 12 ]

Current Secondary Outcome Measures (submitted: March 19, 2013)

• 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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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 ]
  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.

Original Secondary Outcome Measures (submitted: May 23, 2008)

• DAS28-3 (CRP), DAS28-4 (ESR) [ Time Frame: At multiple time ]
• ACR 20, 50, 70, and 90 Responder rates , area under the ACR-N curve at all timepoints. Observed values and changes from baseline of the 7 components of the ACR Core set. [ Time Frame: At multiple time ]
• QOL assessments (SF-36, HAQ-DI, EQ-5D) [ Time Frame: At multiple time ]
• Incidence and severity of AEs and lab test abnormalities, vital signs, ECG [ Time Frame: At multiple time ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison Of 5 CP-690,550 Doses Vs. Placebo, For The Treatment Of Rheumatoid Arthritis In Japan
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Arthritis, Rheumatoid

Intervention

• Drug: Placebo
  Placebo BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  10mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  15mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  1mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  3mg BID, 3 blinded tablets administered BID for 12 weeks
• Drug: CP-690,550
  5mg BID, 3 blinded tablets administered BID for 12 weeks

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Experimental: CP-690,550, 10mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 15mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 1mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 3mg
  Intervention: Drug: CP-690,550
• Experimental: CP-690,550, 5mg
  Intervention: Drug: CP-690,550

Publications *

• Winthrop KL, Curtis JR, Yamaoka K, Lee EB, Hirose T, Rivas JL, Kwok K, Burmester GR. Clinical Management of Herpes Zoster in Patients With Rheumatoid Arthritis or Psoriatic Arthritis Receiving Tofacitinib Treatment. Rheumatol Ther. 2022 Feb;9(1):243-263. doi: 10.1007/s40744-021-00390-0. Epub 2021 Dec 6.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Wang L, Chen C, Kwok K, Biswas P, Shapiro A, Madsen A, Wollenhaupt J. Long-term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme. RMD Open. 2020 Oct;6(3):e001395. doi: 10.1136/rmdopen-2020-001395.
• Panaccione R, Isaacs JD, Chen LA, Wang W, Marren A, Kwok K, Wang L, Chan G, Su C. Characterization of Creatine Kinase Levels in Tofacitinib-Treated Patients with Ulcerative Colitis: Results from Clinical Trials. Dig Dis Sci. 2021 Aug;66(8):2732-2743. doi: 10.1007/s10620-020-06560-4. Epub 2020 Aug 20. Erratum In: Dig Dis Sci. 2020 Oct 10;:
• Suzuki M, Shoji S, Miyoshi S, Krishnaswami S. Model-Based Comparison of Dose-Response Profiles of Tofacitinib in Japanese Versus Western Rheumatoid Arthritis Patients. J Clin Pharmacol. 2020 Feb;60(2):198-208. doi: 10.1002/jcph.1514. Epub 2019 Sep 12.
• Cohen SB, Tanaka Y, Mariette X, Curtis JR, Lee EB, Nash P, Winthrop KL, Charles-Schoeman C, Thirunavukkarasu K, DeMasi R, Geier J, Kwok K, Wang L, Riese R, Wollenhaupt J. Long-term safety of tofacitinib for the treatment of rheumatoid arthritis up to 8.5 years: integrated analysis of data from the global clinical trials. Ann Rheum Dis. 2017 Jul;76(7):1253-1262. doi: 10.1136/annrheumdis-2016-210457. Epub 2017 Jan 31.
• Charles-Schoeman C, Burmester G, Nash P, Zerbini CA, Soma K, Kwok K, Hendrikx T, Bananis E, Fleischmann R. Efficacy and safety of tofacitinib following inadequate response to conventional synthetic or biological disease-modifying antirheumatic drugs. Ann Rheum Dis. 2016 Jul;75(7):1293-301. doi: 10.1136/annrheumdis-2014-207178. Epub 2015 Aug 14. Erratum In: Ann Rheum Dis. 2017 Mar;76(3):611.
• Tanaka Y, Takeuchi T, Yamanaka H, Nakamura H, Toyoizumi S, Zwillich S. Efficacy and safety of tofacitinib as monotherapy in Japanese patients with active rheumatoid arthritis: a 12-week, randomized, phase 2 study. Mod Rheumatol. 2015 Jul;25(4):514-21. doi: 10.3109/14397595.2014.995875.
• Cohen S, Radominski SC, Gomez-Reino JJ, Wang L, Krishnaswami S, Wood SP, Soma K, Nduaka CI, Kwok K, Valdez H, Benda B, Riese R. Analysis of infections and all-cause mortality in phase II, phase III, and long-term extension studies of tofacitinib in patients with rheumatoid arthritis. Arthritis Rheumatol. 2014 Nov;66(11):2924-37. doi: 10.1002/art.38779.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 28, 2010): 318
• Original Estimated Enrollment (submitted: May 23, 2008): 300
• Actual Study Completion Date: July 2010
• Actual Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00687193
• Other Study ID Numbers: A3921040
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Pfizer
• Original Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: March 2013