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 language | English (US) |
|---|---|
| Pages (from-to) | 1811-1820 |
| Number of pages | 10 |
| Journal | Neurology |
| Volume | 89 |
| Issue number | 17 |
| DOIs | |
| State | Published - Oct 24 2017 |
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ASJC Scopus subject areas
- Clinical Neurology
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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 journal › Article
}
TY - JOUR
T1 - A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy
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
PY - 2017/10/24
Y1 - 2017/10/24
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.
UR - http://www.scopus.com/inward/record.url?scp=85032229798&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85032229798&partnerID=8YFLogxK
U2 - 10.1212/WNL.0000000000004570
DO - 10.1212/WNL.0000000000004570
M3 - Article
C2 - 28972192
AN - SCOPUS:85032229798
VL - 89
SP - 1811
EP - 1820
JO - Neurology
JF - Neurology
SN - 0028-3878
IS - 17
ER -