A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy
<br><strong>Objective: </strong>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).</br> <br><strong>Me...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
Wolters Kluwer Health, Inc.
2017
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| _version_ | 1826257876333625344 |
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| author | 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 Tadalafil DMD Study Group Servais, L |
| author2 | Servais. L |
| author_facet | Servais. L 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 Tadalafil DMD Study Group Servais, L |
| author_sort | Victor, RG |
| collection | OXFORD |
| description | <br><strong>Objective: </strong>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).</br>
<br><strong>Methods: </strong>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.</br>
<br><strong>Results: </strong>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.</br>
<br><strong>Conclusions: </strong>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.</br> |
| first_indexed | 2024-03-06T18:25:07Z |
| format | Journal article |
| id | oxford-uuid:07acefc6-f3c1-43d6-aaff-dd314f53221c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:25:07Z |
| publishDate | 2017 |
| publisher | Wolters Kluwer Health, Inc. |
| record_format | dspace |
| spelling | oxford-uuid:07acefc6-f3c1-43d6-aaff-dd314f53221c2022-03-26T09:08:55ZA phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:07acefc6-f3c1-43d6-aaff-dd314f53221cEnglishSymplectic ElementsWolters Kluwer Health, Inc.2017Victor, RGSweeney, HLFinkel, RMcDonald, CMByrne, BEagle, MGoemans, NVandenborne, KDubrovsky, ALTopaloglu, HMiceli, MCFurlong, PLandry, JElashoff, RTadalafil DMD Study GroupServais, LServais. L<br><strong>Objective: </strong>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).</br> <br><strong>Methods: </strong>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.</br> <br><strong>Results: </strong>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.</br> <br><strong>Conclusions: </strong>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.</br> |
| spellingShingle | 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 Tadalafil DMD Study Group Servais, L A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title | A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title_full | A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title_fullStr | A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title_full_unstemmed | A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title_short | A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy |
| title_sort | phase 3 randomized placebo controlled trial of tadalafil for duchenne muscular dystrophy |
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