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A Study To Evaluate The Safety And Efficacy Of Tofacitinib Modified Release Tablets Compared To Tofacitinib Immediate Release Tablets In Adult Patients With Rheumatoid Arthritis

Phase 3
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT02281552
Lead Sponsor
Pfizer
Brief Summary

This is a 12 week study that will evaluate the efficacy and safety of the 11 mg tofacitinib modified release tablet taken once a day in patients with rheumatoid arthritis who continue taking methotrexate. Results for the modified release tablets will be compared to the efficacy and safety of the 5 mg tofacitinib immediate release tablets taken twice a day in patients with rheumatoid arthritis who continue taking methotrexate.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
209
Inclusion Criteria
  • diagnosis of rheumatoid arthritis
  • currently taking a stable dose of methotrexate
  • no evidence of active or latent or inadequately treated tuberculosis
Exclusion Criteria
  • evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic or allergic disease
  • clinically significant infections within the past 6 months

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
tofacitinib modified release tabletTofacitinib-
tofacitinib immediate release tabletTofacitinib-
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (C-Reactive Protein [CRP]) at Week 12Baseline, Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from swollen joint count (SJC) and tender/painful joint count (TJC) using 28 joints count, CRP (milligrams per liter \[mg/L\]) and patient global assessment of disease activity on a 100 millimeter (mm) visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \[less than or equal to\] \<= 3.2 implied low disease activity and greater than (\>) 3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) less than (\<) 2.6 implied remission.

Secondary Outcome Measures
NameTimeMethod
Number of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Week 12Week 12

Participants with 50% improvement in 68-tender and 66-swollen joint counts and 50% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at Week 12Baseline, Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (millimeters per hour \[mm/hr\]) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission.

Number of Participants Achieving an American College of Rheumatology 20 Percent [%] (ACR20) Response at Week 12Week 12

Participants with 20% improvement in 68-tender and 66-swollen joint counts and 20% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Change From Baseline in the Short Form 36 (SF-36) Health Survey Component Scores at Week 12Baseline, Week 12

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were aggregated to derive the two component scores PCS and MCS ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

Number of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Week 12Week 12

Participants with 70% improvement in 68-tender and 66-swollen joint counts and 70% improvement in at least 3 of the 5 measures: patient's global assessment of arthritis, physician global assessment of arthritis, patient's assessment of arthritis pain, health assessment questionnaire-disability index(HAQ-DI) and CRP. Patient's global assessment of arthritis: participant assessed arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Physician global assessment of arthritis: physician judged participants arthritis by 100 mm VAS, score: 0 mm (no arthritis) to 100 mm (extreme arthritis), higher score implied more arthritis. Patient's assessment of arthritis pain: participant assessed arthritis pain by 100 mm VAS, score: 0 mm (no pain) to 100 mm (most severe pain), higher score implied more pain. HAQ-DI: functional disability evaluation, score: 0 (no difficulty) to 3 (extreme difficulty), higher score implied more disability.

Number of Participants With DAS Remission (DAS28-4-CRP <2.6) at Week 12Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. Number of participants with DAS remission (DAS28-4-CRP\<2.6) were reported in this outcome measure.

Number of Participants With Low Disease Activity (DAS28-4-CRP <=3.2) at Week 12Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (CRP) was calculated from SJC and TJC using 28 joints count, CRP (mg/L) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (CRP) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (CRP) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (CRP) \<2.6 implied remission. Number of participants with low disease activity (DAS28-4-CRP\<=3.2) were reported in this outcome measure.

Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12Baseline, Week 12

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. 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 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities.

Number of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ Scores) at Week 12Week 12

HAQ-DI assesses the degree of difficulty a participant has experienced during the past week in 8 categories of daily living activities: dressing/grooming; arising; eating; walking; reach; grip; hygiene; and other activities over past week. Each activity category consisted of 2-3 items. 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 (least difficulty) and 3 (extreme difficulty), where higher scores indicate more difficulty while performing daily living activities. Number of participants with an improvement of at least 0.22 units in HAQ scores from baseline to Week 12 were reported in this outcome measure.

Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at Week 12Baseline, Week 12

SF-36 is a participant reported standardized survey designed to assess generic health related quality of life. It consisted of 36 items evaluating 8 aspects of functional health and well-being: physical functioning, role physical, bodily pain, social functioning, mental health, role emotional, vitality, and general health. The score range for each of the 8 health aspects was from 0 (poor health) to 100 (better health), higher scores indicating good health condition. Scores of 8 health aspects were aggregated to derive the two component scores (physical component scores \[PCS\], mental component scores \[MCS\]) ranging from 0 (worst) to 100 (best), where higher scores indicated good health condition.

Number of Participants With DAS Remission (DAS28-4-ESR <2.6) at Week 12Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<= 3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. Number of participants with DAS remission (DAS28-4-ESR\<2.6) were reported in this outcome measure.

Number of Participants With Low Disease Activity (DAS28-4-ESR <=3.2) at Week 12Week 12

DAS28 is a measure of disease activity in participants with rheumatoid arthritis. DAS28-4 (ESR) was calculated from SJC and TJC using 28 joints count, ESR (mm/hr) and patient global assessment of disease activity on a 100 mm visual analog scale (VAS: scores ranging from 0 mm \[very well\] to 100 mm \[extremely bad\], higher scores indicate worse health condition). Total DAS28-4 (ESR) score range: 0 (none) to 9.4 (extreme disease activity), higher score indicated more disease activity. DAS28-4 (ESR) \<=3.2 implied low disease activity and \>3.2 to \<=5.1 implied moderate disease activity, \>5.1 implied high disease activity, and DAS28-4 (ESR) \<2.6 implied remission. Number of participants with low disease activity (DAS28-4-ESR\<=3.2) were reported in this outcome measure.

Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at Week 12Baseline, Week 12

The FACIT-Fatigue Scale was a participant completed questionnaire consisted of 13 items that assessed fatigue. Each item was scored on a scale of 0 (not at all) to 4 (very much), Total score ranging from 0 (not at all) to 52 (very much), higher scores represented lower level of fatigue.

Change From Baseline in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at Week 12Baseline, Week 12

EQ-5D was a participant completed instrument designed to assess impact on quality of life in terms of a single utility score in five domains: mobility, self-care, usual activities, pain and discomfort, and anxiety and depression with 3 possible answers for each item (1=no problem, 2=moderate problems, 3=severe problems). The 5-dimensional systems are converted into a single index utility score between 0 and 1, where higher score indicated a better health state.

Trial Locations

Locations (36)

National Hospital Organization Toyohashi Medical Center

🇯🇵

Toyohashi, Aichi, Japan

Yamada Rheumatology Clinic

🇯🇵

Matsuyama, Ehime, Japan

Inoue Hospital

🇯🇵

Tohrimachi, Takasaki, Gunma, Japan

Yoshida orthopaedics and rheumatologyclinic

🇯🇵

Morioka, Iwate, Japan

Showa University Hospital

🇯🇵

Shinagawa-ku, Tokyo, Japan

Sugimoto rheumatology and internal medicine clinic

🇯🇵

Fukui, Japan

SHONO Rheumatism Clinic

🇯🇵

Fukuoka, Japan

Sagawa Akira Rheumatology Clinic

🇯🇵

Hokkaido, Japan

Matsubara Mayflower Hospital

🇯🇵

Hyogo, Japan

Yokohama Minami Kyosai Hospital

🇯🇵

Kanagawa, Japan

Kumamoto Orthopaedic Hospital

🇯🇵

Kumamoto, Japan

Hirose Clinic

🇯🇵

Saitama, Japan

National Hospital Organization Sagamihara National Hospital

🇯🇵

Sagamihara, Kanagawa, Japan

Rabbit Clinic

🇯🇵

Saitama, Japan

Osaki Citizen Hospital

🇯🇵

Oosaki, Miyagi, Japan

Soshigayaokura clinic

🇯🇵

Setagaya-ku, Tokyo, Japan

National Hospital Organization Yokohama Medical Center

🇯🇵

Yokohama, Kanagawa, Japan

Sasebo Chuo Hospital

🇯🇵

Sasebo, Nagasaki, Japan

Otsuka Clinic of Rheumatism and Medicine

🇯🇵

Oita, Japan

St. Mary's Hospital

🇯🇵

Kurume, Fukuoka, Japan

Japanese Red Cross Nagoya Daiichi Hospital

🇯🇵

Nagoya, Aichi, Japan

National Hospital Organization Asahikawa Medical Center

🇯🇵

Asahikawa, Hokkaido, Japan

Katayama Orthopaedic Rheumatology Clinic

🇯🇵

Asahikawa, Hokkaido, Japan

Tohoku University Hospital/ Department of Hematology and Rheumatology

🇯🇵

Sendai, Miyagi, Japan

Nagano Red Cross Hospital

🇯🇵

Nagano-shi, Nagano, Japan

National Hospital Organization Nagoya Medical Center

🇯🇵

Nagoya, Aichi, Japan

Gunma Rheumatism Clinic

🇯🇵

Takasaki-shi, Gunma, Japan

Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital

🇯🇵

Hiroshima-city, Hiroshima, Japan

Komagamine Rheumatoid Orthopaedic Clinic

🇯🇵

Morioka, Iwate, Japan

National Hospital Organization Chiba-East Hospital

🇯🇵

Chiba, Japan

National Hospital Organization Ureshino Medical Center

🇯🇵

Ureshino-shi, Saga, Japan

Honjo Rheumatism Clinic

🇯🇵

Takaoka-shi, Toyama, Japan

Miyasato Clinic

🇯🇵

Shunan, Yamaguchi, Japan

National Hospital Organization Kyushu Medical Center

🇯🇵

Fukuoka, Japan

Japanese Red Cross Kyoto Daiichi Hospital

🇯🇵

Kyoto, Japan

Oribe Clinic of Rheumatology and Internal Medicine

🇯🇵

Oita, Japan

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