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

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 11

Inclusion Criteria

• Males with proven DMD ;• Ages 7-14 years inclusive;• Ambulant, defined as baseline 6MWD between 200 and 400 meters inclusive ;• Baseline 6MWD measurements within 20% of the screening 6MWD;• Left ventricular ejection fraction (LVEF) >=50% ;• 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.

Exclusion Criteria

• Symptomatic cardiomyopathy or heart failure (New York Heart Association Class III or IV) ;• Change (initiation, change in type of drug, dose modification, schedule modification, interruption, discontinuation, or reinitiating) in prophylactic treatment for heart failure within 3 months prior to start of study treatment;• Cardiac rhythm disorder defined as sinus rhythm with ectopic contractions or conductance disturbances, or any rhythm other than sinus, observed on screening ECG ;• Use of continuous mechanical ventilator assistance. [Evening use of bi-level positive airway pressure (BPAP) or continuous positive airway pressure (CPAP) therapy is allowed];• Previous treatment with investigational drugs or interventions (including shock training system) within 3 months of the first administration of study medication, or planned use during the study ;• History of participation in gene or cell-based therapy ;• History of antisense oligonucleotide (AON) or stop codon read-through therapy ;• Unable to take orally administered tablets (without chewing, crushing or breaking), as assessed by the investigator ;• Use of L-arginine supplements within 4 weeks (+/- 1 day) of the first administration of study medication ;• 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 (e.g., growth hormone, anabolic steroids including testosterone). Vitamin D, calcium, and combinations thereof will be allowed.;• 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. Patients taking herbal or dietary supplements as defined above with no change in type or dose for 1 month prior to first dose of study drug with no expectation of adding or changing supplements for the 48 week double-blind period may be enrolled. ;• 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 in the judgment of the investigator affect performance on the 6MWD;• Severe behavioral problems, including severe autism or attention deficit disorders, that may in the judgment of the investigator 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, defined as receiving renal dialysis or having a screening serum cystatin C level >= 2.35 mg/L ;• Clinical evidence of cirrhosis ;• Diagnosed with a retinal disorder (for example, hereditary retinal disorders, retinopathy of prematurity);• Have severe hypotension or uncontrolled hypertension as determined by the investigator;• Current treatment with potent CYP3A4 inhibitors, such as antiretroviral therapy (protease inhibitor), systemic ketoconazole, or systemic itraconazole, or chronic use of potent CYP3A4 inducers, such as rifampicin;• Currently receiving treatment with doxazosin, nitrates, or cancer therapy;• Have known allergy to any of the excipients in tadalafil tablets, notably lactose;• Current PDE5 inhibitor therapy or treatment within the past 6 months ;• Other medical condition deemed to place the patient at potential increased risk or reduced adherence to the study protocol ;• Histo

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary efficacy measure is:<br /><br><br /><br>- 6-minute walk distance (6MWD)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary efficacy measures are:<br /><br><br /><br>- North Star Ambulation Assessment (NSAA)<br /><br>- Timed function tests (rise from floor from supine, 10 meter walk/run, 4-stair<br /><br>climb/descend) </p><br>