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Neurology. 2017 Oct 24;89(17):1811-1820. doi: 10.1212/WNL.0000000000004570. Epub 2017 Sep 29.

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

Author information

1
From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and Eli Lilly and Company (D.C.), Indianapolis, IN. Ronald.victor@cshs.org.
2
From the Cedars-Sinai Medical Center (R.G.V.), Los Angeles, CA; University of Florida (H.L.S., B.B., K.V.), Gainesville; Nemours Children's Hospital (R.F.), Orlando, FL; University of California at Davis (C.M.M.), Sacramento; Newcastle University (M.E.), Newcastle Upon Tyne, UK; University Hospitals Leuven (N.G.), Belgium; Instituto de Neurociencias-Fundacion Favaloro (A.L.D.), Buenos Aires, Argentina; Hacettepe University School of Medicine (H.T.), Ankara, Turkey; UCLA (M.C.M., R.E.), Los Angeles, CA; Parent Project Muscular Dystrophy (P.F.), Hackensack, NJ; Eli Lilly Canada, Eli Lilly and Company, Toronto, ON (J.L.); and Eli Lilly and Company (D.C.), Indianapolis, IN.

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·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.

RESULTS:

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.

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.

CLINICALTRIALSGOV IDENTIFIER:

NCT01865084.

CLASSIFICATION OF EVIDENCE:

This study provides Class I evidence that tadalafil does not slow ambulatory decline in 7- to 14-year-old boys with Duchenne muscular dystrophy.

PMID:
28972192
PMCID:
PMC5664308
DOI:
10.1212/WNL.0000000000004570
[Indexed for MEDLINE]
Free PMC Article

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