Background: Givinostat is indicated for Duchenne muscular dystrophy (DMD) treatment in patients aged ≥6 years based on findings from EPIDYS (NCT02851797). Diarrhea has been reported as a common adverse event (AE) in patients treated with givinostat.
Objective: To further characterize diarrhea AEs (severity, time of onset, and duration) following givinostat treatment in EPIDYS.
Methods: Patients received a weight-based starting dose of givinostat (n=118) or placebo (n=61) in addition to standard of care (ie, corticosteroids). The givinostat dose was reduced if moderate to severe diarrhea occurred.
Results: Overall, 44 patients (37.3%) and 12 patients (19.7%) in the givinostat and placebo groups, respectively, experienced ≥1 diarrhea AE. A total of 117 and 16 diarrhea events were reported in each group, respectively. For patients who started on higher (20-70 mg) vs lower (13.3-46.7 mg) givinostat doses, 52.7% (n=29/55) and 22.2% (n=14/63) experienced ≥1 diarrhea AE, respectively. One patient (higher starting givinostat dose) had a dose reduction owing to diarrhea. Most diarrhea AEs were mild; none were reported to be serious. The median (interquartile range [IQR]) time to the first diarrhea AE after starting givinostat was 13.5 (6.0, 31.0) days. The median (IQR) duration of diarrhea events was 6.0 (2.0, 15.0) days. Givinostat was permanently discontinued for 1 patient (study day 223); moderate diarrhea was reported on day 205, which resolved by day 232.
Conclusions: Reports of diarrhea in EPIDYS were generally mild in severity and manageable. In most cases, diarrhea resolved quickly and rarely led to givinostat discontinuation.