Delayed Release Prednisone in PMR

Dinora

Status and phase: Terminated; Phase 2

Conditions: Polymyalgia Rheumatica

Treatments: Drug: Immediate Release (IR) Prednisone; Drug: Delayed-Release (DR) Prednisone

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT02702778

HZNP-PRE-IIS02

Details and patient eligibility

About

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.

Enrollment: 8 patients

Sex: All

Ages: 50+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

8 participants in 3 patient groups

4mg DR-Prednisone

Active Comparator group

Description:

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.

Treatment:

Drug: Delayed-Release (DR) Prednisone

Drug: Immediate Release (IR) Prednisone

7mg DR-Prednisone

Active Comparator group

Description:

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.

Treatment:

Drug: Delayed-Release (DR) Prednisone

Drug: Immediate Release (IR) Prednisone

10mg DR-Prednisone

Active Comparator group

Description:

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.

Treatment:

Drug: Delayed-Release (DR) Prednisone

Drug: Immediate Release (IR) Prednisone