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

Tadalafil DMD Study Group, Giacomo Pietro Comi

Research output: Contribution to journalArticle

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. © 2017 The Author(s).
Original languageEnglish
Pages (from-to)1811-1820
Number of pages10
JournalNeurology
Volume89
Issue number17
DOIs
Publication statusPublished - 2017

Keywords

  • creatine kinase
  • deflazacort
  • dystrophin
  • glucocorticoid
  • placebo
  • prednisolone
  • prednisone
  • tadalafil
  • vasodilator agent, abdominal pain
  • adolescent
  • Article
  • backache
  • child
  • clinical outcome
  • controlled study
  • corticosteroid therapy
  • deterioration
  • diarrhea
  • drug efficacy
  • drug megadose
  • drug safety
  • drug withdrawal
  • Duchenne muscular dystrophy
  • epistaxis
  • fever
  • fracture
  • function test
  • headache
  • heart left ventricle ejection fraction
  • human
  • influenza
  • low drug dose
  • major clinical study
  • male
  • mobilization
  • nausea
  • pain
  • phase 3 clinical trial
  • priapism
  • priority journal
  • rhinopharyngitis
  • side effect
  • six minute walk test
  • treatment duration
  • upper abdominal pain
  • upper respiratory tract infection
  • vomiting
  • area under the curve
  • clinical trial
  • dose response
  • double blind procedure
  • follow up
  • heart left ventricle function
  • heart rate
  • international cooperation
  • lung function test
  • multicenter study
  • Muscular Dystrophy, Duchenne
  • physiology
  • psychology
  • quality of life
  • randomized controlled trial
  • treatment outcome
  • walking, Adolescent
  • Area Under Curve
  • Child
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Follow-Up Studies
  • Glucocorticoids
  • Heart Rate
  • Humans
  • International Cooperation
  • Male
  • Quality of Life
  • Respiratory Function Tests
  • Tadalafil
  • Treatment Outcome
  • Vasodilator Agents
  • Ventricular Function, Left
  • Walking

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