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

Research output: Contribution to journalArticle

19 Citations (Scopus)

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

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Duchenne Muscular Dystrophy
Randomized Controlled Trials
Placebos
Upper Extremity
Tadalafil
Muscular Diseases
Glucocorticoids
Safety

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Victor, R. G., Sweeney, H. L., Finkel, R., McDonald, C. M., Byrne, B., Eagle, M., ... 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

A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. / Victor, Ronald G.; Sweeney, H. Lee; Finkel, Richard; McDonald, Craig M; Byrne, Barry; Eagle, Michelle; Goemans, Nathalie; Vandenborne, Krista; Dubrovsky, Alberto L.; Topaloglu, Haluk; Miceli, M. Carrie; Furlong, Pat; Landry, John; Elashoff, Robert; Cox, David.

In: Neurology, Vol. 89, No. 17, 24.10.2017, p. 1811-1820.

Research output: Contribution to journalArticle

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 2017, 'A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy', Neurology, vol. 89, no. 17, pp. 1811-1820. https://doi.org/10.1212/WNL.0000000000004570
Victor, Ronald G. ; Sweeney, H. Lee ; Finkel, Richard ; McDonald, Craig M ; Byrne, Barry ; Eagle, Michelle ; Goemans, Nathalie ; Vandenborne, Krista ; Dubrovsky, Alberto L. ; Topaloglu, Haluk ; Miceli, M. Carrie ; Furlong, Pat ; Landry, John ; Elashoff, Robert ; Cox, David. / A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. In: Neurology. 2017 ; Vol. 89, No. 17. pp. 1811-1820.
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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.",
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AU - Victor, Ronald G.

AU - Sweeney, H. Lee

AU - Finkel, Richard

AU - McDonald, Craig M

AU - Byrne, Barry

AU - Eagle, Michelle

AU - Goemans, Nathalie

AU - Vandenborne, Krista

AU - Dubrovsky, Alberto L.

AU - Topaloglu, Haluk

AU - Miceli, M. Carrie

AU - Furlong, Pat

AU - Landry, John

AU - Elashoff, Robert

AU - Cox, David

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N2 - 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.

AB - 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.

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