- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02710591
Rimeporide in Patients With Duchenne Muscular Dystrophy (RIM4DMD)
A Phase Ib, Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Ascending Oral Doses of Rimeporide in Patients With Duchenne Muscular Dystrophy
Study Overview
Detailed Description
This study is designed as a phase Ib, multicenter, european, open label study to evaluate the safety and tolerability and biomarkers of a new drug, rimeporide, in boys aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).
Rimeporide will be taken orally for 4 weeks, three times a day. Dose will be adapted to body weight. The study will enrol 20 patients with DMD, aged 6 to 14 years. 4 dose levels will be tested, in 4 different cohorts with 5 patients taking the drug at each dose level.
During the study, there will be 6 visits in the Hospital over a maximum of 10 weeks. At each visit, patients will undergo safety examinations including vital signs, physical and neurological examinations, ECG, safety and hematology, biochemistry and urinalysis, concomitant treatments review, and any symptoms and side effects review. In addition, blood samples will be withdrawn for the evaluation of Rimeporide in plasma. Finally, additional blood & urine samples will be collected to explore efficacy markers. Patients will also undergo 2 NMR (at screening and End of study) to develop non invasive biomarkers for further investigations in DMD patients.
The decision to progress to the next higher dose will be made after safety and tolerability data are reviewed for the preceding dose for 5 patients by SMC and determined that it is safe to proceed to the next dose level.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ile De France
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Paris, Ile De France, France, 75012
- I-Motion - Hôpital Armand Trousseau
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Milano, Italy, 20132
- San Raffaele Hospital
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Barcelona, Spain, 08041
- Santa Creu i Sant Pau Hospital
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London, United Kingdom, WC1N 1EH
- UCL Institute of Child Health and Great Ormond Street Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Duchenne muscular dystrophy genetically confirmed;
- Males between 6 and 14 years old;
- Able to walk independently at least 75 meters;
- Patients on a stable dose of corticosteroids at least 6 months prior to baseline;
- Patients able to swallow capsules size 4 according to the parents and investigator opinion;
- Willing and able to comply with all protocol requirements and procedures;
- Signed informed consents by the parent(s)/legal guardian(s);
- France only: Affiliated to or a beneficiary of a social security system
Exclusion Criteria:
- Patients with significant renal disease or impairment, with Glomerular Filtration Rate estimated using plasma cystatin C level using the Filler formula less than 90ml/min/1.73m2
- Current or history of liver disease or impairment,
- History of any significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory, coagulation disease, unstable cardiac or respiratory disease
- Acute illness within 4 weeks of the first administration of study medication which may interfere with study assessments;
- Significant change of dosage and/or dosing regimens for corticosteroids planned for the duration of study medication;
- Use of beta blockers / and ACEI or ARB unless at stable dose for at least 3 months prior to baseline;
- Use of Proton Pump Inhibitors unless at a stable dose for at least 3 months prior to baseline
- Use of aldosterone antagonists (i.e. spironolactone, eplerenone) within 3 months prior to first administration of study medication;
- Use of anticoagulants, antithrombotics or antiplatelet agents,
- Use of antibiotics with predominant renal secretion (e.g., cephalosporins), immunosuppressive agents exception corticosteroids, continuous treatment with non-steroidal, anti-inflammatory drugs (NSAIDs), or lithium;
- Previous treatment with idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication;
- Previous treatment with investigational drugs within 4 weeks (or 7 half-life if longer than 4 weeks) of the first administration of study medication including placebo;
- A baseline QTc>450msec,or history of risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome);
- LVEF≤ 45% at screening or within the past 6 months and/or history of acute heart failure;
- Ventilator dependent;
- Known individual hypersensitivity to any of the ingredients/excipients of the study medication;
- Patients with specific contraindication to MRI (e.g.: metallic foreign body, claustrophobia, etc.).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Rimeporide
Multiple oral doses of rimeporide ranging from 50 to 300 mg will be administered three times a day (TID) for a total of 4 weeks. 4 ascending dose levels will be studied sequentially in ascending order. Rimeporide is provided as hard gel 25 mg or 50 mg capsules. Each patient will participate in only 1 dose cohort. 5 patients are expected to be recruited in each cohort through all participating sites. |
Cohort 1: 50 mg TID in patients with a body weight ≤ 30kg at Baseline and 75 mg TID in patients with a body weight > 30kg at Baseline Cohort 2: 100mg TID in patients with a body weight ≤ 30kg at baseline and 150 mg TID in patients with a body weight > 30kg at Baseline Cohort 3: 150 mg TID in patients with a body weight ≤ 30kg at baseline and 200 mg TID in patients with a body weight > 30kg at Baseline Cohort 4: 200 mg TID in patients with a body weight ≤ 30kg at Baseline and 300 mg TID mg TID in patients with a body weight > 30kg at Baseline
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Number of Participants With Adverse Events
Time Frame: up to 6 weeks from first administration
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Observations are given for the safety population (all patients who received at least one dose of study drug). Categorical data are presented with the number of subjects with at least one event for the following selections:
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up to 6 weeks from first administration
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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PK Profile of Rimeporide - Cmax
Time Frame: 4 week study treatment
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PK samples were collected according to the following schedule:
Finally, at week 4 (Day 28) after the last dose:
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4 week study treatment
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Florence Porte-Thomé, R&D Director EspeRare
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EspeRare_RIM_001
- 2015-002530-50 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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