Rimeporide in Patients With Duchenne Muscular Dystrophy
Condition: Muscular Dystrophy, Duchenne
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Rimeporide
Intervention description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: Male
Minimum age: 6 Years
Maximum age: 14 Years
Healthy volunteers: No
Keywords: Rimeporide

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).
    

Eligibility criteria:

        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.).