Rimeporide in Patients With Duchenne Muscular Dystrophy
Condition: Muscular Dystrophy, Duchenne
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Study type: Interventional
Phase: Phase 1

Summary: 
      In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and
      sodium in the muscles cells which is thought to be important in the damage which occurs
      overtime. Sodium/proton type 1 exchanger (NHE-1) inhibition is an innovative pathway that has
      proved to efficiently prevent the accumulation of muscle damage (inflammation and fibrosis)
      in animal models of muscular dystrophies and heart failure. Based on prior safety and
      efficacy results in animal and humans, NHE-1 inhibition with Rimeporide represents a new
      therapeutic approach with no restriction on age and on genetic subtypes which could be
      combined to other treatments that restore or augment dystrophin.This study examines the
      safety and tolerability and effects on the muscles of rimeporide, in patients aged 6 to 14
      years with Duchenne Muscular Dystrophy (DMD).
    

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      samples will be withdrawn for the evaluation of Rimeporide in plasma.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.
    

Intervention name(s): Rimeporide
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): EMD 87580
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Rimeporide