polymyalgia rheumatica MedDRA version: 16.1 Level: PT Classification code 10036099 Term: Polymyalgia rheumatica System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Interventions
Trade Name: Lodotra 1 mg modified release tablets
Pharmaceutical Form: Modified-release tablet
INN or Proposed INN: prednisone
Other descriptive name: PREDNISONE
Concentration unit: mg milligram(s)
Sponsors
Mundipharma Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or females, 50 years of age or older who provided written informed consent and are not under a legal protection system or deprived of liberty by judicial or administrative measures. 2. Females less than one year post-menopausal must have a negative serum or urine pregnancy test recorded prior to the first dose of study medication, be non-lactating, and willing to use adequate and highly effective methods of contraception throughout the study. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as sterilisation, implants, injectables, combined oral contraceptives, some IUDs (Intrauterine Device, hormonal), sexual abstinence or vasectomised partner). 3. Subjects newly diagnosed with polymyalgia rheumatica and previously untreated with glucocorticoids for PMR. The diagnosis of polymyalgia rheumatica must be confirmed by all of the following criteria: • New onset bilateral shoulder pain or new onset bilateral shoulder and hip girdle pain. • PMR VAS score over the last 24 hours before the Screening Visit = 50 (on a 0 - 100 scale). • Morning stiffness duration of > 45 min on the day before the Screening Visit. • Acute phase response shown by elevated C-reactive protein (CRP; = 2 times ULN). 4. Subjects willing and able to participate in all aspects of the study and comply with the use of study medication. Criteria for Entry into the Open-label Extension Phase (Re-randomisation): 1. Inclusion criteria no. 1, 2 and 4 still fulfilled. 2. None of the exclusion criteria fulfilled. 3. Subject demonstrates = 70% improvement in PMR VAS and = 70% reduction in the duration of morning stiffness from baseline (Visit 2). 4. Investigator considers subject eligible for entry into open-label phase of the study. 5. Subject is willing to enter the open-label phase of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 400 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 400
Exclusion criteria
Exclusion criteria: 1. Females who are pregnant (positive ß-hCG test) or lactating. 2. Subjects with any contraindication/history of hypersensitivity to predniso(lo)ne or other ingredients. 3. Significant renal impairment (serume creatinine > 150 µmol/L). 4. Significant hepatic impairment (ALT, AST and GGT > 2.5 ULN). 5. Subjects suffering from another disease which requires glucocorticosteroid treatment. Topical glucocorticosteroids, e.g. intra-nasal or inhaled glucocorticosteroids are allowed but should be kept at a stable dose throughout the study. 6. Continued use of systemic glucocorticoids within 4 weeks prior to the Screening Visit. 7. Joint injections with glucocorticoids within 6 weeks prior to the Screening Visit. 8. Subjects who require treatment with non-permitted concomitant therapies. 9. Evidence of clinically significant cardiovascular, renal, hepatic, gastrointestinal or psychiatric disease at the time of screening, as determined by medical history, clinical laboratory tests, ECG results, and physical examination, that would place the subject at risk upon exposure to the study medication or that may confound the analysis and/or interpretation of the study results. 10. Active alcohol or drug abuse. 11. Subjects suffering from giant cell arteritis, late onset rheumatoid arthritis or other inflammatory rheumatoid diseases. 11a. Subjects who have pre study documented evidence of raised RF and ACPA will be excluded from study entry. 12. Subjects suffering from drug-induced myalgia. 13. Subjects suffering from fibromyalgia 14. Subjects suffering from systemic lupus erythemathosus. 15. Subjects suffering from neurological conditions, e.g. Parkinson’s disease. 16. Subjects suffering from active cancer. 17. Subjects suffering from an active infection. 18. Subjects who participated in a clinical research study involving a new chemical entity or an experimental drug within 30 days prior to the Screening Visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show that treatment with Lodotra® (starting dose of 15 mg daily), administered in the evening, is non-inferior to treatment with prednisone IR (starting dose of 15 mg daily), administered in the morning, with regards to the percentage of complete responders to treatment 4 weeks after randomisation.;Secondary Objective: 1. To demonstrate superiority of Lodotra® (starting dose of 15 mg daily) to prednisone IR (starting dose of 15 mg daily) in the core phase. 2. To compare Lodotra® (starting dose of 15 mg daily) and prednisone IR (starting dose of 15 mg daily) in the core phase by means of: Level of response, Pain/Fatigue/PMR VAS, Duration of morning stiffness, Lab values for CRP and erythrocyte sedimentation rate (ESR), subject questionnaires (Health assessment questionnaire disability index (HAQ-DI); Quality of life: Short Form (SF)-36 physical component summary (PCS) and SF-36 mental component summary (MCS); EuroQol (EQ)-5D), IL-6 levels. 3. To assess the potential for dose sparing effects between Lodotra® and prednisone IR in the extension phase of the study. 4. To assess safety and tolerability in the core phase of the study and long-term safety from the extension phase by assessing AEs, vital signs (including weight), laboratory data, and electrocardiograms (ECGs).;Primary end point(s): The primary efficacy variable is the percentage of complete responders at week 4 of the double-blind core phase. Complete response is defined as all three of the following: 1. = 70% improvement from baseline in PMR visual analogue scale (VAS). 2. = 70% reduction from baseline in the duration of morning stiffness (MST). 3. = 70% reduction from baseline in C-reactive protein (CRP) value or CRP value < 2 times upper limit of normal (ULN).;Timepoint(s) of evaluation of this end point: after data base lock of the double-blind core phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Double-Blind Core Phase, key secondary variables: • The change from baseline in PMR VAS score over the last 24 hours at week 4. • The change from baseline in duration of morning stiffness at week 4. • The change from baseline (Visit 1, Screening) in CRP at week 4. • The percentage of complete responders at weeks 1 and 2. Double-Blind Core Phase, additional secondary variables: • The percentage of subjects at each level of response at each visit. • The percentage of subjects with = 70% improvement (response) from baseline in PMR VAS score over the last 24 hours at each visit. • The percentage of subjects with = 70% reduction (response) from baseline in duration of morning stiffness at each visit. • The percentage of subjects with = 70% reduction (response) from baseline (Visit 1, screening) in CRP or within 2 times the upper limit of normal (ULN) at each visit. • The percentage of subjects with = 70% improvement (response) from baseline in global pain VAS score over the last 24 hours at each visit. • The percentage of subjects with = 70% improvement (response) from baseline in shoulder pain VAS score over the last 24 hours at each visit. • The percentage of subjects with = 70% improvement (response) from baseline in fatigue VAS score over the last 24 hours at each visit. • The change from baseline in PMR VAS score over the last 24 hours at Weeks 1 and 2. • The change from baseline in PMR VAS score at awakening at each visit. • The change from baseline in duration of morning stiffness at weeks 1 and 2. • The change from baseline in global pain VAS score over the last 24 hours at each visit. • The change from baseline in global pain VAS score at awakening at each visit. • The change from baseline in shoulder pain VAS score over the last 24 hours at each visit. • The change from baseline in fatigue VAS score over the last 24 hours at each visit. • The change from baseline (Visit 1, Screening) in CRP at weeks 1 and 2. • The | — |
Countries
Czech Republic, Denmark, Germany, Hungary, Italy, Spain, United Kingdom
Contacts
Public ContactClinical Lead
Mundipharma Research GmbH & Co. KG
Outcome results
None listed