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

Lookup NU author(s): Dr Michelle Eagle

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Abstract

© 2017 The Author(s). 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.

Publication metadata

Author(s): 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, Cox D

Publication type: Article

Publication status: Published

Journal: Neurology

Year: 2017

Volume: 89

Issue: 17

Pages: 1811-1820

Print publication date: 24/10/2017

Online publication date: 29/09/2017

Acceptance date: 02/04/2016

Date deposited: 07/11/2017

ISSN (print): 0028-3878

ISSN (electronic): 1526-632X

Publisher: Lippincott Williams and Wilkins

URL: .https:/​/​doi.​org/​10.​1212/​WNL.​0000000000004570

DOI: 10.1212/WNL.0000000000004570

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