A Study of Tadalafil for Duchenne Muscular Dystrophy
Condition: Muscular Dystrophy, Duchenne
MeSH terms: Muscular Dystrophies; Muscular Dystrophy, Duchenne
Intervention: Tadalafil; Placebo
Intervention description: Administered orally
Intervention MeSH terms: Tadalafil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 331.0
Sex: Male
Minimum age: 7 Years
Maximum age: 14 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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