A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy

<br><strong>Objective: </strong>To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).</br> <br><strong>Me...

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Príomhchruthaitheoirí: Victor, RG, Sweeney, HL, Finkel, R, McDonald, CM, Byrne, B, Eagle, M, Goemans, N, Vandenborne, K, Dubrovsky, AL, Topaloglu, H, Miceli, MC, Furlong, P, Landry, J, Elashoff, R, Tadalafil DMD Study Group, Servais, L
Rannpháirtithe: Servais. L
Formáid: Journal article
Teanga:English
Foilsithe / Cruthaithe: Wolters Kluwer Health, Inc. 2017
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Achoimre:<br><strong>Objective: </strong>To conduct a randomized trial to test the primary hypothesis that once-daily tadalafil, administered orally for 48 weeks, lessens the decline in ambulatory ability in boys with Duchenne muscular dystrophy (DMD).</br> <br><strong>Methods: </strong>Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg·kg−1·d−1, tadalafil 0.6 mg·kg−1·d−1, or placebo. The primary efficacy measure was 6-minute walk distance (6MWD) after 48 weeks. Secondary efficacy measures included North Star Ambulatory Assessment and timed function tests. Performance of Upper Limb (PUL) was a prespecified exploratory outcome.</br> <br><strong>Results: </strong>Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 ± 9.3 m with placebo, 64.7 ± 9.8 m with low-dose tadalafil (p = 0.307 vs placebo), and 59.1 ± 9.4 m with high-dose tadalafil (p = 0.538 vs placebo). Tadalafil also had no effect on secondary outcomes. In boys >10 years of age, total PUL score and shoulder subscore declined less with low-dose tadalafil than placebo. Adverse events were consistent with the known safety profile of tadalafil and the DMD disease state.</br> <br><strong>Conclusions: </strong>Tadalafil did not lessen the decline in ambulatory ability in boys with DMD. Further studies should be considered to confirm the hypothesis-generating upper limb data and to determine whether ambulatory decline can be slowed by initiation of tadalafil before 7 years of age.</br>