Efficacy and Tolerability of Idebenone in Boys With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy

A Phase IIa Double Blind, Randomised, Placebo Controlled, Single Centre Study at the University of Leuven to Assess the Efficacy and Tolerability of Idebenone in 8 - 16 Year Old Males With Cardiac Dysfunction Associated With Duchenne Muscular Dystrophy

Idebenone is a synthetic analogue of coenzyme Q10 and is a powerful antioxidant and essential constituent of the process of energy production on the cellular level. It can protect mitochondria from oxidative damage and boost their impaired function. It is thought that this mechanism will slow decline in heart function that is part of the disease process of Duchenne Muscular Dystrophy (DMD). It is possible that patients may benefit in terms of muscle strength and respiratory function. This pilot trial is designed to investigate this.

Inclusion Criteria:

• Patients 8 - 16 years of age at time of enrolment
• Male
• Presence of cardiac involvement/dysfunction, defined by abnormal peak systolic strain in left ventricle (LV) inferolateral wall
• Confirmed diagnosis of DMD (out of frame dystrophin gene deletion OR absent/<5% dystrophin protein on muscle biopsy; clinical picture consistent of typical DMD)
• If on chronic glucocorticosteroids treatment (deflazacort, prednisone) for DMD (or any other disease) (i.e. concomitant medication): dosage must be stable (unchanged) 6 months prior to inclusion
• If on chronic medication for DMD associated cardiomyopathy (β-blocker, diuretics): dosage must be stable (unchanged) 3 months prior to inclusion
• Ability to provide reproducible repeat quantitative muscle testing (QMT) upper limb score within 15% of first assessment score (at Visit1/Day 1 versus Screening Visit

Exclusion Criteria:

• Symptomatic cardiomyopathy or heart failure
• Asymptomatic but severe cardiac dysfunction on baseline (Screening) evaluation: Fractional shortening (FS) < 20% and/or Ejection fraction (EF) < 40%
• Use of ACE-inhibitors
• Previous history of ventricular arrhythmias (other than isolated ventricular extrasystole); ventricular arrhythmias presented at Screening
• Previous (6 months or less) participation in any other therapeutic trial for DMD
• Use of coenzymeQ10, idebenone, creatine, glutamine, oxatomide, or any herbal medicines within the last 6 months
• History of significant concomitant illness or significant impairment of renal or hepatic function
• Known individual hypersensitivity to idebenone