A Study of Tadalafil for Duchenne Muscular Dystrophy

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tadalafil for Duchenne Muscular Dystrophy

The main purpose of this study is to determine if tadalafil can slow the decline in walking ability of boys who have Duchenne muscular dystrophy (DMD). The study will also assess the safety of tadalafil and any side effects that might be associated with it in boys who have DMD. Participants will receive study treatment (tadalafil or placebo) for the first 48 weeks of the study, and can then continue into an open label extension (OLE) that consists of two periods during which all participants will receive tadalafil. In OLE period 1, all participants will receive tadalafil for 48 weeks. Participants completing OLE period 1 will continue into OLE period 2 and will receive tadalafil for at least another 48 weeks.

Inclusion Criteria:

• Ambulant males with Duchenne muscular dystrophy (DMD) confirmed by typical clinical presentation (onset of clinical signs or symptoms before 6 years of age supported by an elevated serum creatinine kinase level, and ongoing difficulty with walking) together with either a record of a genetic confirmation of the DMD diagnosis, or a record of muscle biopsy showing near-complete dystrophin deficiency (excluding revertant fibers)
• Receiving systemic corticosteroids for a minimum of 6 months immediately prior to screening, with no significant change in total daily dosage or dosing regimen (except those adjusting for weight changes) for a minimum of 3 months immediately prior to screening and a reasonable expectation that total daily dosage and dosing regimen will not change significantly (except for adjustments for weight) for the duration of the study
• Able to complete the six minute walk distance (6MWD) test with results within 20% of each other at a minimum of 2 pre-randomization assessments
• Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiogram
• Written informed consent from parents/legal guardian will be obtained prior to any study procedure being performed. In addition, the child may be required to give documented assent, if capable.

Exclusion Criteria:

• Symptomatic cardiomyopathy or heart failure
• Change in prophylactic treatment for heart failure within 3 months prior to start of study treatment
• Cardiac rhythm disorder
• History of participation in gene or cell-based therapy , or antisense oligonucleotide or stop codon read-through therapy
• Unable to take orally administered tablets
• Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength within 3 months prior to the start of study treatment (for example, growth hormone, anabolic steroids including testosterone)
• New or changed treatment with herbal or dietary supplements being taken with an expectation of an effect on muscle strength or function during 1 month prior to first dose of study drug
• Surgery that might have an effect on muscle strength or function within 3 months before study entry or planned surgery at any time during the study
• Evidence of a lower limb injury that may affect performance on the 6MWD
• Severe behavioral problems, including severe autism or attention deficit disorders, that may interfere with completion of the 6MWD
• Any contraindication to tadalafil (use of any form of organic nitrate, either regularly and/or intermittently, or known serious hypersensitivity to tadalafil)
• History of significant renal insufficiency or clinical evidence of cirrhosis
• Have known allergy to any of the excipients in tadalafil tablets, notably lactose
• Current Phosphodiesterase Type 5 (PDE5) inhibitor therapy or treatment within the past 6 months