A Study of Tadalafil for Duchenne Muscular Dystrophy

Inclusion Criteria:

• Ambulant males with Duchenne muscular dystrophy (DMD) confirmed by typical clinicalpresentation (onset of clinical signs or symptoms before 6 years of age supported byan elevated serum creatinine kinase level, and ongoing difficulty with walking)together with either a record of a genetic confirmation of the DMD diagnosis, or arecord of muscle biopsy showing near-complete dystrophin deficiency (excludingrevertant fibers)

• Receiving systemic corticosteroids for a minimum of 6 months immediately prior toscreening, with no significant change in total daily dosage or dosing regimen (exceptthose adjusting for weight changes) for a minimum of 3 months immediately prior toscreening and a reasonable expectation that total daily dosage and dosing regimen willnot change significantly (except for adjustments for weight) for the duration of thestudy

• Able to complete the six minute walk distance (6MWD) test with results within 20% ofeach 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 anystudy procedure being performed. In addition, the child may be required to givedocumented assent, if capable.

Exclusion Criteria:

• Symptomatic cardiomyopathy or heart failure

• Change in prophylactic treatment for heart failure within 3 months prior to start ofstudy treatment

• Cardiac rhythm disorder

• History of participation in gene or cell-based therapy , or antisense oligonucleotideor stop codon read-through therapy

• Unable to take orally administered tablets

• Use of any pharmacologic treatment, other than corticosteroids, that might have aneffect on muscle strength within 3 months prior to the start of study treatment (forexample, growth hormone, anabolic steroids including testosterone)

• New or changed treatment with herbal or dietary supplements being taken with anexpectation of an effect on muscle strength or function during 1 month prior to firstdose of study drug

• Surgery that might have an effect on muscle strength or function within 3 monthsbefore 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, eitherregularly 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