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

Arthritis, Rheumatoid Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00413660
• Other study ID #: A3921025
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2006
• Last updated: January 14, 2013
• Start date: January 2007
• Est. completion date: August 2008

Study information

• Verified date: January 2013
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 509
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Active rheumatoid arthritis

• Inadequate response to stably dosed methotrexate

Exclusion Criteria:

• Current therapy with any DMARD or biologic other than methotrexate

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid

Intervention

Drug:
• CP-690,550
4 blinded tablets administered BID
• CP-690,550
4 blinded tablets administered BID
• CP-690,550
4 blinded tablets administered BID
• CP-690,550
4 blinded tablets administered BID
• CP-690,550
4 blinded tablets administered BID
• CP-690,550
Oral tablets

Other:
• placebo
Placebo

Locations

Country	Name	City	State
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Buenos Aires
Argentina	Pfizer Investigational Site	Capital Federal	Buenos Aires
Brazil	Pfizer Investigational Site	Curitiba	PR
Brazil	Pfizer Investigational Site	Curitiba	PR
Brazil	Pfizer Investigational Site	Goiania	GO
Brazil	Pfizer Investigational Site	Goiânia	GO
Brazil	Pfizer Investigational Site	Sao Paulo	SP
Brazil	Pfizer Investigational Site	São Paulo	SP
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Sofia
Bulgaria	Pfizer Investigational Site	Sofia 1606
Chile	Pfizer Investigational Site	Providencia	RM
Chile	Pfizer Investigational Site	Santiago	RM
Chile	Pfizer Investigational Site	Santiago
Chile	Pfizer Investigational Site	Viña Del Mar	V Region
Czech Republic	Pfizer Investigational Site	Brno
Czech Republic	Pfizer Investigational Site	Ceske Budejovice
Czech Republic	Pfizer Investigational Site	Praha 11 - Chodov
Czech Republic	Pfizer Investigational Site	Praha 2
Czech Republic	Pfizer Investigational Site	Praha 4
Czech Republic	Pfizer Investigational Site	Zlin
Hungary	Pfizer Investigational Site	Budapest
Hungary	Pfizer Investigational Site	Komarom
Hungary	Pfizer Investigational Site	Szolnok
Hungary	Pfizer Investigational Site	Veszprem
Mexico	Pfizer Investigational Site	Mexico	DF
Mexico	Pfizer Investigational Site	Morelia	Michoacan
Poland	Pfizer Investigational Site	Bialystok
Poland	Pfizer Investigational Site	Bialystok
Poland	Pfizer Investigational Site	Grudziadz
Poland	Pfizer Investigational Site	Poznan
Poland	Pfizer Investigational Site	Sopot
Poland	Pfizer Investigational Site	Warszawa
Poland	Pfizer Investigational Site	Wroclaw
Slovakia	Pfizer Investigational Site	Bratislava
Slovakia	Pfizer Investigational Site	Piestany
Slovakia	Pfizer Investigational Site	Zilina
Spain	Pfizer Investigational Site	Guadalajara
Spain	Pfizer Investigational Site	Madrid
Spain	Pfizer Investigational Site	Santiago de Compostela	A Coruña
Spain	Pfizer Investigational Site	Sevilla
Sweden	Pfizer Investigational Site	Jonkoping
Sweden	Pfizer Investigational Site	Umea
Turkey	Pfizer Investigational Site	Ankara
Turkey	Pfizer Investigational Site	Istanbul
Turkey	Pfizer Investigational Site	Izmir
Turkey	Pfizer Investigational Site	Izmir
United States	Pfizer Investigational Site	Albany	New York
United States	Pfizer Investigational Site	Austin	Texas
United States	Pfizer Investigational Site	Binghamton	New York
United States	Pfizer Investigational Site	Boston	Massachusetts
United States	Pfizer Investigational Site	Charlotte	North Carolina
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dallas	Texas
United States	Pfizer Investigational Site	Dayton	Ohio
United States	Pfizer Investigational Site	Debary	Florida
United States	Pfizer Investigational Site	Denver	Colorado
United States	Pfizer Investigational Site	Dubuque	Iowa
United States	Pfizer Investigational Site	Frederick	Maryland
United States	Pfizer Investigational Site	Gilbert	Arizona
United States	Pfizer Investigational Site	Greenville	South Carolina
United States	Pfizer Investigational Site	Hot Springs	Arkansas
United States	Pfizer Investigational Site	Lake Mary	Florida
United States	Pfizer Investigational Site	Mesquite	Texas
United States	Pfizer Investigational Site	Newark	Delaware
United States	Pfizer Investigational Site	Ocala	Florida
United States	Pfizer Investigational Site	Onalaska	Wisconsin
United States	Pfizer Investigational Site	Orlando	Florida
United States	Pfizer Investigational Site	Philladelphia	Pennsylvania
United States	Pfizer Investigational Site	Raleigh	North Carolina
United States	Pfizer Investigational Site	Rockford	Illinois
United States	Pfizer Investigational Site	Rockford	Illinois
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Seattle	Washington
United States	Pfizer Investigational Site	Tacoma	Washington
United States	Pfizer Investigational Site	Tacoma	Washington
United States	Pfizer Investigational Site	Tampa	Florida
United States	Pfizer Investigational Site	Upland	California
United States	Pfizer Investigational Site	West Reading	Pennsylvania
United States	Pfizer Investigational Site	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Chile,  Czech Republic,  Hungary,  Mexico,  Poland,  Slovakia,  Spain,  Sweden,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at Week 12	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).	Week 12	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response	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.	Week 2, 4, 6, 8, 16, 20, 24/Early Termination (ET)	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response	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.	Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response	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.	Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Area Under the Numeric Index of American College of Rheumatology Response (ACR-n) Curve	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.	Baseline up to Week 2, 4, 6, 8, 12	No
Secondary	Tender Joints Count (TJC)	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Tender Joints Count (TJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Swollen Joints Count (SJC)	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Swollen Joints Count (SJC) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Patient Assessment of Arthritis Pain	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Patient Assessment of Arthritis Pain at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Patient Global Assessment (PtGA) of Arthritis	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Patient Global Assessment (PtGA) of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Physician Global Assessment of Arthritis	Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Physician Global Assessment of Arthritis at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	Physician global assessment of arthritis was measured on a 0 to 100 mm VAS, where 0 mm = very good and 100 mm = very bad.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Health Assessment Questionnaire-Disability Index (HAQ-DI)	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	C-Reactive Protein (CRP)	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Change From Baseline in C-Reactive Protein (CRP) at Week 2, 4, 6, 8, 12, 16, 20 and 24/ET	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	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	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.	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Percentage of Participants With Categorization of Disease Improvement Based on DAS28-3 (CRP)	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.	Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	Percentage of Participants With Disease Remission Based on DAS28-3 (CRP)	DAS28-3 (CRP) defined remission was classified as a score of <2.6.	Week 2, 4, 6, 8, 12, 16, 20, 24/ET	No
Secondary	36-Item Short-Form Health Survey (SF-36)	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).	Baseline, Week 12, 24/ET	No
Secondary	Change From Baseline in 36-Item Short-Form Health Survey (SF-36) at Week 12 and 24/ET	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).	Baseline, Week 12, 24/ET	No
Secondary	Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility Score	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.	Baseline, Week 12, 24/ET	No
Secondary	Change From Baseline in Euro Quality of Life-5 Dimentions (EQ-5D) - Health State Profile Utility at Week 12 and 24/ET	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.	Baseline, Week 12, 24/ET	No
Secondary	Medical Outcome Study- Sleep Scale (MOS-SS)	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.	Baseline, Week 2, 12, 24/ET	No
Secondary	Change From Baseline in Medical Outcome Study- Sleep Scale (MOS-SS) at Week 2, 12 and 24/ET	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.	Baseline, Week 2, 12, 24/ET	No
Secondary	Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale	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.	Baseline, Week 2, 12, 24/ET	No
Secondary	Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale at Week 2, 12 and 24/ET	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.	Baseline, Week 2, 12, 24/ET	No

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