A Study of Tadalafil for Duchenne Muscular Dystrophy

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