Clinical Trial: Rimeporide in Patients With Duchenne Muscular Dystrophy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: 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

Brief 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 Summary:

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 In addition, blood samples will be withdrawn for the evaluation of Rimeporide in plasma.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.

Sponsor: EspeRare Foundation

Current Primary Outcome:

• To evaluate the incidence of the Adverse Events [AEs] and Serious adverse event [SAEs] which might occur after multiple oral administrations of rimeporide in pediatric patients with DMD [ Time Frame: at 4 weeks of treatment ]
  Number of patients with AEs and SAEs related or not to the study treatment
• To evaluate the causality of the Adverse Events [AEs] and Serious adverse event [SAEs] which might occur after multiple oral administrations of rimeporide in pediatric patients with DMD [ Time Frame: at 4 weeks of treatment ]
  Number of patients with AEs and SAEs possibly or probably related to study treatment
• To evaluate the outcome of the Adverse Events [AEs] and Serious adverse event [SAEs] which might occur after multiple oral administrations of rimeporide in pediatric patients with DMD [ Time Frame: at 4 weeks of treatment ]
  Outcomes of AEs and SAEs possibly or probably related to study treatment

Original Primary Outcome: Same as current

Current Secondary Outcome:

• To evaluate the Maximum Plasma Concentration of rimeporide in plasma in pediatric patients with DMD [ Time Frame: at 4 week study treatment ]
  Maximum Plasma Concentration [Cmax]
• To evaluate the Area Under the Curve of rimeporide in plasma in pediatric patients with DMD [ Time Frame: at 4 week study treatment ]
  Area Under the Curve [AUC]
• To evaluate the Time to concentration peak of rimeporide in plasma in pediatric patients with DMD [ Time Frame: at 4 week study treatment ]
  Time to concentration peak [Tmax]
• To evaluate the Elimination half- life of rimeporide in plasma in pediatric patients with DMD [ Time Frame: at 4 week study treatment ]
  Elimination Half life [T1/2]

Original Secondary Outcome: Same as current

Information By: EspeRare Foundation

Dates:
Date Received: January 26, 2016
Date Started: March 2016
Date Completion: March 2017
Last Updated: October 5, 2016
Last Verified: October 2016