Clinical trial NCT02702778: Delayed Release Prednisone in PMR
Official title: A Randomized, Open-label, Dose-ranging Study of Oral Delayed Release Prednisone in Patients With Untreated Polymyalgia Rheumatic (PMR)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Polymyalgia Rheumatica
Keywords: Polymyalgia Rheumatica (PMR)
Lead sponsor: Dinora, Inc.
Sponsor class: OTHER
Collaborators: name: Analgesic Solutions
name: PharPoint Research, Inc.
First posted: 2016-03-09
Enrollment: 8
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Diagnosis of PMR:

   1. 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
   2. All participants must have PMR in the opinion of the PI
2. Are over 50 years old.
3. No or stable NSAID or analgesic therapy for at least 7 days.
4. 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.
5. 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:

1. Oral glucocorticoid treatment for more than 1 week within the previous month
2. Parenteral glucocorticoid treatment within the last month
3. Pregnancy and/or lactation
4. Inflammatory diseases such as inflammatory bowel disease, colitis, asthma, rheumatoid arthritis
5. 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
6. Other auto-immune diseases
7. Synovitis or polymyositis
8. Positive Cyclic Citrullinated Peptide Antibodies (CCP)
9. Muscle weak and elevated creatinine phosphokinase (CPK)
10. Cancer (patients with a history of basal cell carcinoma or cancer-free for \> 5 years are allowed)
11. 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
12. Significant renal disease (creatinine greater than150 µmol/L)
13. Significant hepatic impairment (ALT/AST greater than twice upper limit of normal)
14. 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.
15. Use of any other systemic glucocorticoids including inhalants during the screening and treatment phase of the study; chronic intranasal or ophthalmic corticosteroids are allowed.
16. Participation in a clinical trial of an investigational drug within the past 30 days
17. Working night-time shift employee
18. Jet lag (i.e. airplane travel)
19. Unable to provide informed consent

Primary outcomes:
measure: Change of the severity of morning stiffness from baseline to end of study (28days)
timeFrame: Assessed daily from screening through End of Study visit, 28 days total
Secondary outcomes:
measure: Relative reduction in the duration of morning stiffness (minutes)
timeFrame: Assessed daily from screening through End of Study visit, an average of 2 months
measure: Relative IL-6 treatment response.
timeFrame: Assessed at Baseline, Day 14, and Day 28
measure: Changes in plasma IL-6 compared with changes in the severity of morning stiffness
timeFrame: Through study completion, a total of 3 assessments over 28days
measure: Patient reported outcomes in accordance with the OMERACT PMR objectives
timeFrame: Through study completion, an average of 2 months.
measure: Performance characteristics of additional clinical measures of disease outcome.
timeFrame: Through study completion, an average of 2 months
Other outcomes:
measure: Changes in PMR Activity Score (PMRAS) following treatment with DR prednisone and IR prednisone
timeFrame: Through study completion, an average of 2 months
Locations:
city: Miami
country: United States
facility: Clinical Research Site
state: Florida
city: Mineola
country: United States
facility: Clinical Research Site
state: New York
city: Duncansville
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Site 2
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Site
state: Pennsylvania
city: Spokane
country: United States
facility: Clinical Research Site
state: Washington
Study officials:
References: