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

Rheumatoid Arthritis Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Parallel-group, Phase 3 Study To Demonstrate Non-inferiority For The Efficacy Of A Once Daily Dose Of Tofacitinib Modified Release Tablet To A Twice Daily Dose Of The Immediate Release Tablet In Adult Patients With Rheumatoid Arthritis On Background Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02281552
• Other study ID #: A3921215
• Secondary ID: TOFACITINIB QD P
• Status: Completed
• Phase: Phase 3
• Start date: November 18, 2014
• Est. completion date: March 15, 2017

Study information

• Verified date: March 2018
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: March 15, 2017
• Est. primary completion date: March 15, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Tofacitinib
tofacitinib modified release 11 mg tablet administered once time a day for 12 weeks
• Tofacitinib
tofacitinib immediate release 5 mg tablet administered twice a day for 12 weeks

Locations

Country	Name	City	State
Japan	Katayama Orthopaedic Rheumatology Clinic	Asahikawa	Hokkaido
Japan	National Hospital Organization Asahikawa Medical Center	Asahikawa	Hokkaido
Japan	National Hospital Organization Chiba-East Hospital	Chiba
Japan	Sugimoto rheumatology and internal medicine clinic	Fukui
Japan	National Hospital Organization Kyushu Medical Center	Fukuoka
Japan	SHONO Rheumatism Clinic	Fukuoka
Japan	Hiroshima Red Cross Hospital & Atomic-bomb Survivors Hospital	Hiroshima-city	Hiroshima
Japan	Sagawa Akira Rheumatology Clinic	Hokkaido
Japan	Matsubara Mayflower Hospital	Hyogo
Japan	Yokohama Minami Kyosai Hospital	Kanagawa
Japan	Kumamoto Orthopaedic Hospital	Kumamoto
Japan	St. Mary's Hospital	Kurume	Fukuoka
Japan	Japanese Red Cross Kyoto Daiichi Hospital	Kyoto
Japan	Yamada Rheumatology Clinic	Matsuyama	Ehime
Japan	Komagamine Rheumatoid Orthopaedic Clinic	Morioka	Iwate
Japan	Yoshida orthopaedics and rheumatologyclinic	Morioka	Iwate
Japan	Nagano Red Cross Hospital	Nagano-shi	Nagano
Japan	Japanese Red Cross Nagoya Daiichi Hospital	Nagoya	Aichi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi
Japan	Oribe Clinic of Rheumatology and Internal Medicine	Oita
Japan	Otsuka Clinic of Rheumatism and Medicine	Oita
Japan	Osaki Citizen Hospital	Oosaki	Miyagi
Japan	National Hospital Organization Sagamihara National Hospital	Sagamihara	Kanagawa
Japan	Hirose Clinic	Saitama
Japan	Rabbit Clinic	Saitama
Japan	Sasebo Chuo Hospital	Sasebo	Nagasaki
Japan	Tohoku University Hospital/ Department of Hematology and Rheumatology	Sendai	Miyagi
Japan	Soshigayaokura clinic	Setagaya-ku	Tokyo
Japan	Showa University Hospital	Shinagawa-ku	Tokyo
Japan	Miyasato Clinic	Shunan	Yamaguchi
Japan	Honjo Rheumatism Clinic	Takaoka-shi	Toyama
Japan	Gunma Rheumatism Clinic	Takasaki-shi	Gunma
Japan	Inoue Hospital	Tohrimachi, Takasaki	Gunma
Japan	National Hospital Organization Toyohashi Medical Center	Toyohashi	Aichi
Japan	National Hospital Organization Ureshino Medical Center	Ureshino-shi	Saga
Japan	National Hospital Organization Yokohama Medical Center	Yokohama	Kanagawa

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment- Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs were events between first dose of study drug and up to 12 weeks that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non- serious adverse events.	Baseline up to 12 weeks
Other	Number of Participants With Clinically Significant Laboratory Test Abnormalities	Criteria: lipids(cholesterol[CH] milligrams/deciliter[mg/dL] >1.3*upper limit normal(ULN), high-density lipoprotein CH mg/dL <0.8*lower limit normal(LLN), Low-density lipoprotein CH mg/dL >1.2* ULN, triglycerides mg/dL >1.3*ULN); neutrophil count(NC) <1000 cells/cubic milliliters(mm^3), platelet counts(PC) <100,000 P/mm^3, lymphocyte counts(LC) <500 L/mm^3, any single (aspartate transaminase elevation(ASTE)/alanine transaminase elevation(ALTE) >=3*ULN, hemoglobin(Hb) value <8.0 grams(g)/dL or >=2 g/dL below baseline, any serum creatinine(SC) increase(inc) >50% or inc >0.5 mg/dL over the average of screening(OAS) and baseline values(BV), 2 sequential ASTE/ALTE>=3*ULN with total bilirubin value(TBV) >=2*ULN, ASTE/ALTE >=3*ULN, ASTE/ALTE >=5*ULN, Hb <8.0 g/dL or decrease of >30% from BV, PC <75,000 P/mm^3, NC <1000 cells/mm^3, LC <500 L/mm^3, confirmed inc in SC >50% OAS and BV and detection of hepatitis B virus-deoxyribonucleic acid(HBV-DNA) by the two sequential quantitative tests.	Baseline up to 12 weeks
Primary	Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (C-Reactive Protein [CRP]) at 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.	Baseline, Week 12
Secondary	Change From Baseline in Disease Activity Score in 28 Joints Using 4 Variables (DAS28-4) (Erythrocyte Sedimentation Rate [ESR]) at 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.	Baseline, Week 12
Secondary	Number of Participants Achieving an American College of Rheumatology 20 Percent [%] (ACR20) Response at Week 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.	Week 12
Secondary	Number of Participants Achieving an American College of Rheumatology 50% (ACR50) Response at Week 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.	Week 12
Secondary	Number of Participants Achieving an American College of Rheumatology 70% (ACR70) Response at Week 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.	Week 12
Secondary	Number of Participants With DAS Remission (DAS28-4-CRP <2.6) at Week 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.	Week 12
Secondary	Number of Participants With DAS Remission (DAS28-4-ESR <2.6) at 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 (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.	Week 12
Secondary	Number of Participants With Low Disease Activity (DAS28-4-CRP <=3.2) at Week 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.	Week 12
Secondary	Number of Participants With Low Disease Activity (DAS28-4-ESR <=3.2) at 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 (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.	Week 12
Secondary	Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at 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.	Baseline, Week 12
Secondary	Number of Participants Achieving an Improvement of at Least 0.22 Units in Health Assessment Questionnaire (HAQ Scores) at 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 with an improvement of at least 0.22 units in HAQ scores from baseline to Week 12 were reported in this outcome measure.	Week 12
Secondary	Change From Baseline in the Short Form 36 (SF-36) Health Survey Domain Scores at 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.	Baseline, Week 12
Secondary	Change From Baseline in the Short Form 36 (SF-36) Health Survey Component Scores at 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.	Baseline, Week 12
Secondary	Change From Baseline in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale Scores at 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.	Baseline, Week 12
Secondary	Change From Baseline in the European Quality of Life - 5 Dimensions Questionnaire (EQ-5D) Scores at 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.	Baseline, Week 12

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