Confirmed Safety of Deutetrabenazine for Tardive Dyskinesia in a 2-Year Open-Label Extension Study

Background: Deutetrabenazine was efficacious and safe in treating tardive dyskinesia (TD) in the 12-week ARM-TD and AIM-TD studies.
Objective: To evaluate the long-term safety and tolerability of deutetrabenazine in patients with TD at 2 years.
Methods: Patients who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study that comprised a 6-week titration period and a long-term maintenance phase. All patients restarted/started deutetrabenazine 12 mg/day, titrating up to a maximum total daily dose of 48 mg/day. Incidence of adverse events (AEs), serious AEs (SAEs), and AEs leading to withdrawal, dose reduction, or dose suspension were assessed. Exposure-adjusted incidence rates (EAIRs; incidence/patient-years) were used to compare AE frequencies for long-term treatment with those for short-term treatment (ARM-TD and AIM-TD).  
Results: 343 patients from the parent studies were included in the analysis (111 placebo, 232 deutetrabenazine), with 331.4 patient-years of exposure. Through Week 106, EAIRs of AEs were comparable to or lower than those observed with short-term treatment, including AEs of interest (akathisia/restlessness [long-term EAIR: 0.02; short-term EAIR range: 0–0.25], anxiety [0.09; 0.13–0.21], depression [0.09; 0.04–0.13], diarrhea [0.06; 0.06–0.34], parkinsonism [0.01; 0–0.08], somnolence/sedation [0.09; 0.06–0.81], and suicidality [0.02; 0–0.13]). The frequency of SAEs (EAIR 0.15) was comparable with short-term placebo (0.33) and deutetrabenazine (range 0.06–0.33). AEs leading to withdrawal (0.08), dose reduction (0.17), and dose suspension (0.06) were uncommon.
Conclusions: The long-term safety profile of deutetrabenazine was consistent with the parent studies, demonstrating tolerability for long-term use in TD patients.