Prednisone Timed-Release Tablet (TRT) Study: Modified-Release (MR) Formulation of Prednisone Compared to Standard Immediate-Release (IR) Prednisone in Participants With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The objective of this study is to investigate if low doses of prednisone MR formulation, given at night and, with active drug release at 2 am, are more effective in controlling joint stiffness, and other disease symptoms of rheumatoid arthritis than standard IR prednisone given in the morning.

Official Title
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A New Timed-Release Tablet Formulation of Prednisone Compared to Standard Prednisone in Patients With Rheumatoid Arthritis- A Randomized, Multi-Centre, Double-Blind, Active Controlled Study With Open Extension on the New Drug Only

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MR Prednisone
* Drug: IR Prednisone
* Drug: Placebo - MR Prednisone
* Drug: Placebo - IR Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active disease (inflammatory signs, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) Stable condition Stable basic treatments Morning stiffness on previous treatment with standard prednisone (below or equal to 10 mg per day) greater than or equal to (>/=) 45 minutes Exclusion Criteria: All contra-indications for glucocorticoids Pregnancy Concomitant treatment with biologics Intra-articular injections or synovectomy within the previous 4 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MR Prednisone<br>Participants will receive MR prednisone at bed time and placebo matching to IR prednisone in the morning. Total duration of double blind treatment will be 12 weeks. | Drug: MR Prednisone<br>* Participants will receive tablets containing MR prednisone (to achieve the appropriate dose of 3-10 milligrams [mg] prednisone per day) at bed time.<br>Drug: Placebo - IR Prednisone<br>* Participants will receive placebo matching to IR prednisone tablet in the morning.<br>|
| Active Comparator: IR Prednisone<br>Participants will receive IR prednisone in the morning and placebo matching to MR prednisone at bed time. Total duration of double blind treatment will be 12 weeks. | Drug: IR Prednisone<br>* Participants will receive tablets containing IR prednisone (to achieve the appropriate dose of 3-10 mg prednisone per day) in the morning.<br>Drug: Placebo - MR Prednisone<br>* Participants will receive placebo matching to MR prednisone tablet at bed time.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in Duration of Morning Stiffness at Week 12 | Duration of morning stiffness was defined as the time elapsed (in minutes) between the time of usual awakening (even if not in the morning) and the time the participant was able to resume normal activities without stiffness. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative Change From Baseline in 28-Joint Disease Activity Score (DAS28) at Week 12 | DAS28 calculated from the number of swollen joints (SJC) and painful joints (PJC) using the 28 joints count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hour]) and patient's global assessment (PGA) of disease activity (participant rated arthritis activity assessment with transformed scores ranging 0 to 10; higher scores indicated greater affectation due to disease activity). Total DAS28 score range from 0 to approximately 10. DAS28 less than or equal to (≤) 3.2 = low disease activity, DAS28 greater than (>) 3.2 to 5.1 = moderate to high disease activity, and DAS28 >5.1 = severe disease activity. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 
| Percentage of Participants With Recurrence of Joint Stiffness at Week 12 | Participants recorded the status of recurrence of joint stiffness (Yes/No) in diary data. Percentage of participants who selected Yes for recurrence of joint stiffness, are reported. | Week 12 | 
| Relative Change From Baseline in Pain Intensity at Week 12 | Participants assessed pain intensity on a 100 millimeter (mm) visual analog scale (VAS), where 0 mm = no pain, 100 mm = worst pain. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 
| Relative Change From Baseline in Quality of Sleep at Week 12 | Participants assessed quality of sleep on a 100 mm VAS, where 0 mm = very good, 100 mm = very bad. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 
| Relative Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 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. Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 
| Relative Change From Baseline in Short-Form 36 (SF36) Mental Component Score (MCS) at Week 12 | SF-36 is a standardized survey evaluating 8 domains of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a domain was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 
| Relative Change From Baseline in SF36 Physical Component Score (PCS) at Week 12 | SF-36 is a standardized survey evaluating 8 aspects of functional health and wellbeing: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. The score for a domain was an average of the individual question scores, which were scaled 0-100 (100=highest level of functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning). Relative (percent) change = ([value at Week 12 minus value at Baseline] divided by [value at baseline]) multiplied by 100. | Baseline, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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active disease, morning stiffness of joints, nighttime application of prednisone, modified release prednisone