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The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study
Journal article   Open access   Peer reviewed

The Safety of Deutetrabenazine for Chorea in Huntington Disease: An Open-Label Extension Study

Samuel Frank, Claudia Testa, Mary C. Edmondson, Jody Goldstein, Elise Kayson, Blair R. Leavitt, David Oakes, Christine O'Neill, Christina Vaughan, Jacquelyn Whaley, …
CNS drugs, Vol.36(11), pp.1207-1216
11/01/2022
DOI: 10.1007/s40263-022-00956-8
PMCID: PMC9653309
PMID: 36242718
url
https://doi.org/10.1007/s40263-022-00956-8View
Published (Version of record) Open Access

Abstract

Background Deutetrabenazine is approved in the USA, China, Australia, Israel, Brazil, and South Korea for the treatment of chorea associated with Huntington disease. Objective We aimed to evaluate the long-term safety and tolerability of deutetrabenazine for the treatment of Huntington disease. Methods This open-label, single-arm, multi-center study included patients who completed a double-blind study (Rollover) and patients who converted overnight from a stable tetrabenazine dose (Switch). Exposure-adjusted incidence rates (adverse events per person-year) were calculated. Efficacy was analyzed using a stable post-titration timepoint (8 weeks). Changes in the Unified Huntington's Disease Rating Scale total motor score and total maximal chorea score from baseline to week 8, as well as those from week 8 to week 145 (or the last visit on the study drug if that occurred earlier), were evaluated as both efficacy and safety endpoints during the study. Results Of 119 patients (Rollover, n = 82; Switch, n = 37), 100 (84%) completed >= 1 year of treatment. End-of-study exposure-adjusted incidence rates for adverse events in Rollover and Switch, respectively, were: any, 2.57 and 4.02; serious, 0.11 and 0.14; leading to dose suspension, 0.05 and 0.04. Common adverse events (>= 4% either cohort) included somnolence (Rollover, 20%; Switch, 30%), depression (32%; 22%), anxiety (27%; 35%), insomnia (23%; 16%), and akathisia (6%; 11%). Adverse events of interest included suicidality (9%; 5%) and parkinsonism (4%; 8%). Mean dose at week 8 was 38.1 mg (Rollover) and 36.5 mg (Switch). Mean dose across cohorts after titration was 37.6 mg; at the final visit, mean dose across cohorts was 45.7 mg. Patients showed minimal change in the Unified Huntington's Disease Rating Scale total maximal chorea scores with stable dosing from weeks 8-145 or at the end of treatment, but total motor score increased versus week 8 (mean change [standard deviation]: 8.2 [11.9]). There were no unexpected adverse events upon drug withdrawal, and mean (standard deviation) total maximal chorea scores increased 4.7 (4.6) units from week 8 to 1-week follow-up. Conclusions Adverse events observed with long-term deutetrabenazine exposure were consistent with previous studies. Reductions in chorea persisted over time. Upon treatment cessation, there was no unexpected worsening of chorea.
 Psychiatry Clinical Neurology Life Sciences & Biomedicine Neurosciences & Neurology Pharmacology & Pharmacy Science & Technology

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