Tadalafil in Boys with Duchenne Muscular Dystrophy (LVJJ study)
Research type
Research Study
Full title
A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial of Tadalafil for Duchenne Muscular Dystrophy
IRAS ID
131755
Contact name
Saleel Chandratre
Contact email
Sponsor organisation
Eli Lilly and Company
Eudract number
2013-001194-25
ISRCTN Number
n/a
Research summary
Duchenne muscular dystrophy (DMD) is a life limiting, muscle-wasting disease typically diagnosed in young boys, for which there are no approved disease-specific treatments. Gene therapy and stem cell transplants have yielded limited clinical progress.
In the absence of pharmacotherapy most children lose the ability to walk by the age of 13. Corticosteroids are the only pharmacological intervention that have been shown in randomized, placebo-controlled trials to slow the progressive decline in muscle strength and function, delaying the loss of ambulation by 2 years or more (Moxley et al., 2010).
Based on available data from an on-going study (Nelson et al., 2013; NCT01580501, unpublished data;), single doses of Tadalafil (0.5 mg/kg or 1.0 mg/kg) restore normal exercise-induced skeletal muscle blood flow responses in boys with DMD receiving corticosteroids. Tadalafil is a selective, reversible PDE5 inhibitor that is currently approved for the treatment of erectile dysfunction. Whether these early clinical findings translate to a clinically relevant benefit with respect to ambulatory function in children afflicted with DMD is an urgent and unanswered question.
The proposed LVJJ study will enrol boys who are 7-14 years old, ambulatory (able to walk) and are receiving treatment with corticosteroids.
The study is divided into 2 phases:
DOUBLE-BLIND TREATMENT Phase – This phase includes screening period (4 weeks) following which all eligible patients will be randomly assigned to one of three treatment arms (placebo, Tadalafil 0.3 mg/kg, or Tadalafil 0.6 mg/kg) in a 1:1:1 ratio. The treatment period is 48 weeks.OPEN-LABEL EXTENSION Phase - Patients who completed the Double-Blind Treatment Period of the study can participate in a 48-week, open-label extension study where all patients will receive active treatment with Tadalafil.
Study assessments will include: motor function assessment tests (eg. walking, stair climbing, upper limb performance), breathing assessment (spiromentry) eye examination, ECG, ECHO, blood and urine tests.
REC name
Yorkshire & The Humber - Leeds East Research Ethics Committee
REC reference
13/YH/0285
Date of REC Opinion
25 Sep 2013
REC opinion
Further Information Favourable Opinion