Comparison of Safety and Tolerability of Deutetrabenazine During Titration and Maintenance in Patients with Tardive Dyskinesia

BackgroundDeutetrabenazine is approved to treat tardive dyskinesia (TD) in adults and is titrated weekly by 6 mg/day, from 12 to 48 mg/day, based on dyskinesia control and tolerability. This analysis compared the safety of deutetrabenazine during titration versus maintenance.MethodsSafety was assessed during titration versus maintenance using integrated data from two 12-week placebo-controlled studies (ARM-TD and AIM-TD) and the open-label extension study. Rates were compared for overall and serious adverse events (AEs), AEs leading to discontinuation, treatment-related AEs, common AEs (≥4%), and specific AEs (parkinsonism, suicidal ideation, akathisia, restlessness).ResultsIn titration versus maintenance, AE rates with placebo (n=130) were: overall, 43.1% vs 25.4%; serious, 4.6% vs 2.3%; leading to discontinuation, 3.1% vs 0; treatment-related, 26.9% vs 10.0%. For placebo, common AEs during titration were somnolence, headache, nausea, fatigue, and dry mouth; none occurred during maintenance. In titration versus maintenance, AE rates in fixed-dose deutetrabenazine 12–36 mg (n=216) were: overall, 33.3–38.9% vs 22.2–29.2%; serious, 2.8–6.9% vs 0–1.4%; leading to discontinuation, 2.8–5.6% vs 0; treatment-related, 8.3–16.7% vs 8.3–13.9%. For fixed-dose deutetrabenazine, common AEs during titration were headache, diarrhea, nasopharyngitis, depression, hypertension, and dry mouth; headache was the only common AE during maintenance. In titration versus maintenance, AE rates with flexible-dose deutetrabenazine (n=168) were: overall, 49.4% vs 32.7%; serious, 3.6% vs 2.4%; leading to discontinuation, 2.4% vs 0.6%. For flexible-dose deutetrabenazine, the only common AE during titration was somnolence; none occurred during maintenance. Rates of parkinsonism, suicidal ideation, akathisia, and restlessness were low and comparable in titration and maintenance.ConclusionsDeutetrabenazine was well-tolerated, with AE rates similar to placebo during both phases; AE rates were higher during titration and decreased during maintenance.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel