Delayed Release Prednisone in PMR

Study Overview
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Brief Summary
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A four-week, randomized, controlled, open-label trial of DR prednisone in which patients receive in period 1 one of three-night time doses of treatment (4mg, 7mg or 10mg) for two weeks followed in period 2 by treatment with 15mg IR prednisone in the morning for two weeks. Period 1 is randomized and open-label and period 2 is open label. Before enrollment and randomization patient diagnosis and responsiveness to 15mg IR prednisone in the morning is established. 45 patients will be randomized, 15 patients in each treatment arm.

Official Title
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A Randomized, Open-label, Dose-ranging Study of Oral Delayed Release Prednisone in Patients With Untreated Polymyalgia Rheumatic (PMR)

Conditions
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Polymyalgia Rheumatica

Intervention / Treatment
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* Drug: Delayed-Release (DR) Prednisone
* Drug: Immediate Release (IR) Prednisone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of PMR: All participants must meet the Bird criteria (7): 3 or more of the following features are required to make the diagnosis. Bilateral shoulder pain/stiffness Onset of symptoms <2 weeks Initial Erythrocyte Sedimentation Rate (ESR) >40 mm/h Stiffness >1 h Age >65 years Depression and/or weight loss Bilateral upper arm tenderness All participants must have PMR in the opinion of the PI Are over 50 years old. No or stable NSAID or analgesic therapy for at least 7 days. Currently active disease defined by a C-reactive protein (CRP) at least 5mg/L, or ESR at least 29mm in one hour measured at the screening visit or within the previous week. Respond to one week of 15 mg IR prednisone and one week washout (patient worsens). Response will be measured as: >70% reduction in morning stiffness severity at the end of the first week with a >80% return of morning stiffness severity in the second week (screening procedure). This screening procedure can also be assessed in patients who have taken up to one week of >15 mg IR prednisone prior to seeing the investigator for the study, so long as informed consent is obtained before the wash-out period and all other inclusion criteria are met. Exclusion Criteria: Oral glucocorticoid treatment for more than 1 week within the previous month Parenteral glucocorticoid treatment within the last month Pregnancy and/or lactation Inflammatory diseases such as inflammatory bowel disease, colitis, asthma, rheumatoid arthritis Co-existent giant cell arteritis; patients with headache, visual symptoms or jaw claudication suggestive of giant cell arteritis will not be included in the study Other auto-immune diseases Synovitis or polymyositis Positive Cyclic Citrullinated Peptide Antibodies (CCP) Muscle weak and elevated creatinine phosphokinase (CPK) Cancer (patients with a history of basal cell carcinoma or cancer-free for > 5 years are allowed) Severe active infection including herpes or other viral or bacterial infection(s), treatment with antibiotics within the past 6 weeks or have or had a history of tuberculosis Significant renal disease (creatinine greater than150 µmol/L) Significant hepatic impairment (ALT/AST greater than twice upper limit of normal) Immunization with live vaccines within 8 weeks before the first administration of the study drug or plan to have an immunization with a live vaccine within 2 weeks after the last administration of study drug. Use of any other systemic glucocorticoids including inhalants during the screening and treatment phase of the study; chronic intranasal or ophthalmic corticosteroids are allowed. Participation in a clinical trial of an investigational drug within the past 30 days Working night-time shift employee Jet lag (i.e. airplane travel) Unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 50 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 4mg DR-Prednisone<br>Subjects in this arm will receive a night-time dose of 4mg delayed-release prednisone for two weeks followed by treatment with 15mg IR-prednisone in the morning for two weeks. | Drug: Delayed-Release (DR) Prednisone<br>* delayed release prednisone<br>* Other names: RAYOS;Drug: Immediate Release (IR) Prednisone<br>* standard prednisone<br>|
| Active Comparator: 7mg DR-Prednisone<br>Subjects in this arm will receive a night-time dose of 7mg delayed-release prednisone for two weeks followed by treatment with 15mg IR-prednisone in the morning for two weeks. | Drug: Delayed-Release (DR) Prednisone<br>* delayed release prednisone<br>* Other names: RAYOS;Drug: Immediate Release (IR) Prednisone<br>* standard prednisone<br>|
| Active Comparator: 10mg DR-Prednisone<br>Subjects in this arm will receive a night-time dose of 10mg delayed-release prednisone for two weeks followed by treatment with 15mg IR-prednisone in the morning for two weeks. | Drug: Delayed-Release (DR) Prednisone<br>* delayed release prednisone<br>* Other names: RAYOS;Drug: Immediate Release (IR) Prednisone<br>* standard prednisone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the severity of morning stiffness from baseline to end of study (28days) | To determine the relative reduction in the severity of morning stiffness of three night time doses (4mg, 7mg, and 10mg) of DR prednisone after 2 weeks compared to the reduction after treatment with IR prednisone15mg in the morning for 2 weeks in newly diagnosed PMR patients (with no evidence of other systemic inflammatory diseases such as RA) who are known to be responsive to standard treatment with IR prednisone15mg in the morning. This will be assessed using a 10cm Visual Analog Scale (VAS). | Assessed daily from screening through End of Study visit, 28 days total | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative reduction in the duration of morning stiffness (minutes) | This will be assessed via a questionnaire. | Assessed daily from screening through End of Study visit, an average of 2 months | 
| Relative IL-6 treatment response. |  | Assessed at Baseline, Day 14, and Day 28 | 
| Changes in plasma IL-6 compared with changes in the severity of morning stiffness |  | Through study completion, a total of 3 assessments over 28days | 
| Patient reported outcomes in accordance with the OMERACT PMR objectives |  | Through study completion, an average of 2 months. | 
| Performance characteristics of additional clinical measures of disease outcome. | Additional characteristics such as pain and fatigue will be assessed using a 10cm Visual Analog Scale (VAS). | Through study completion, an average of 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polymyalgia Rheumatica (PMR)