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

Ronald G. Victor, H. Lee Sweeney, Richard Finkel, Craig M McDonald, Barry Byrne, Michelle Eagle, Nathalie Goemans, Krista Vandenborne, Alberto L. Dubrovsky, Haluk Topaloglu, M. Carrie Miceli, Pat Furlong, John Landry, Robert Elashoff, David Cox

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22 Scopus citations

Abstract

Objective: 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). Methods: Three hundred thirty-one participants with DMD 7 to 14 years of age taking glucocorticoids were randomized to tadalafil 0.3 mg kg21 d21, tadalafil 0.6 mg kg21 d21, 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. Results: Tadalafil had no effect on the primary outcome: 48-week declines in 6MWD were 51.0 6 9.3 m with placebo, 64.7 6 9.8 m with low-dose tadalafil (p 5 0.307 vs placebo), and 59.1 6 9.4 m with high-dose tadalafil (p 5 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1811-1820
Number of pages10
JournalNeurology
Volume89
Issue number17
DOIs
StatePublished - Oct 24 2017

ASJC Scopus subject areas

  • Clinical Neurology

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    Victor, R. G., Sweeney, H. L., Finkel, R., McDonald, C. M., Byrne, B., Eagle, M., Goemans, N., Vandenborne, K., Dubrovsky, A. L., Topaloglu, H., Miceli, M. C., Furlong, P., Landry, J., Elashoff, R., & Cox, D. (2017). A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology, 89(17), 1811-1820. https://doi.org/10.1212/WNL.0000000000004570