Objective: To compare safety of DTBZ in titration vs maintenance using data from two 12-wk placebo (PBO)-controlled studies (ARM-TD and AIM-TD) and an open-label extension (OLE) study.

Background: DTBZ is approved to treat TD in adults. DTBZ is titrated weekly by 6mg/d, from 12 to 48mg/d based on dyskinesia control and tolerability.

Method: Safety was assessed during titration vs maintenance using integrated data from ARM-TD, AIM-TD, and through OLE Wk 15. 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).

Results: In titration vs maintenance, AE rates with PBO (n=131) were: overall, 42.7% vs 25.2%; serious, 4.6% vs 2.3%; leading to discontinuation, 3.1% vs 0; treatment-related, 26.7% vs 9.9%. For PBO, common AEs during titration were somnolence (6.9%), headache (6.1%), nausea (5.3%), fatigue (4.6%), and dry mouth (4.6%); no common AEs occurred during maintenance. In titration vs maintenance, AE rates in fixed-dose DTBZ 12–36mg groups (n=221) were: overall, 32.4–40.5% vs 21.9–28.4%; serious, 2.7–6.8% vs 0–1.4%; leading to discontinuation, 2.7–5.4% vs 0; treatment-related, 8.1–16.2% vs 8.2–13.5%. For fixed-dose DTBZ, common AEs during titration were headache (2.7–6.8%), diarrhea (1.4–5.4%), nasopharyngitis (1.4–4.1%), depression (0–4.1%), hypertension (0–4.1%), and dry mouth (0–4.1%); headache (0–4.1%) was the only common AE during maintenance. In titration vs maintenance, AE rates with flexible-dose DTBZ (n=169) were: overall, 49.1% vs 32.5%; serious, 3.6% vs 2.4%; leading to discontinuation, 2.4% vs 1.2%; treatment-related, 31.4% vs 12.4%. For flexible-dose DTBZ, the only common AE during titration was somnolence (11.2%); there were no common AEs during maintenance. Rates of specific AEs were low and comparable in titration and maintenance (ranges for all groups in both periods: parkinsonism, 0–1.4%; suicidal ideation, 0–2.7%; akathisia, 0–1.8%; restlessness, 0–1.4%).

Conclusion: In patients with TD treated with DTBZ, AE rates were generally higher during titration and decreased during maintenance, providing important context for the dosing schedule to providers and patients. DTBZ was generally well tolerated, with AE rates similar to PBO during both phases.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparison-of-safety-and-tolerability-of-deutetrabenazine-dtbz-during-titration-and-maintenance-in-patients-with-tardive-dyskinesia-td/