Safety of Deutetrabenazine for the Treatment of Tardive Dyskinesia and Chorea Associated with Huntington Disease.

Autor: Frank S; Beth Israel Deaconess Medical Center/Harvard Medical School, 330 Brookline Ave., Kirstein 228, Boston, MA, 02215, USA. sfrank2@bidmc.harvard.edu., Anderson KE; Georgetown University, Washington, DC, USA., Fernandez HH; Cleveland Clinic, Cleveland, OH, USA., Hauser RA; University of South Florida Parkinson's Disease and Movement Disorders Center, Tampa, FL, USA., Claassen DO; Vanderbilt University Medical Center, Nashville, TN, USA., Stamler D; Teva Branded Pharmaceutical Products R&D, Inc., La Jolla, CA, USA., Factor SA; Emory University, Atlanta, GA, USA., Jimenez-Shahed J; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Barkay H; Teva Pharmaceutical Industries Ltd., Netanya, Israel., Wilhelm A; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA., Alexander JK; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA., Chaijale N; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA., Barash S; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA., Savola JM; Teva Pharmaceuticals International GmbH, Basel, Switzerland., Gordon MF; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA., Chen M; Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, USA.
Jazyk: angličtina
Zdroj: Neurology and therapy [Neurol Ther] 2024 Jun; Vol. 13 (3), pp. 655-675. Date of Electronic Publication: 2024 Apr 01.
DOI: 10.1007/s40120-024-00600-1
Abstrakt: Introduction: Deutetrabenazine is a vesicular monoamine transporter 2 inhibitor used to treat tardive dyskinesia (TD) and chorea associated with Huntington disease (HD). To enhance detection of safety signals across individual trials, integrated safety analyses of deutetrabenazine in TD and HD chorea were conducted.
Methods: For TD, safety data were integrated from two 12-week pivotal studies (ARM-TD and AIM-TD) and through week 15 of the open-label extension (OLE) study (RIM-TD). Data were analyzed by deutetrabenazine treatment group and placebo. For HD, safety data were integrated from the 12-week pivotal study (First-HD) and through week 15 of the OLE study (ARC-HD) for patients previously receiving placebo. Integrated deutetrabenazine data were compared with placebo from the pivotal study.
Results: For TD, deutetrabenazine (n = 384) was generally well tolerated compared with placebo (n = 130). Adverse event (AE) incidence was numerically higher in the response-driven deutetrabenazine vs the fixed-dose deutetrabenazine and placebo groups, respectively (any AE, 59.5% vs 44.4-50.0% and 53.8%; treatment-related AE, 38.1% vs 18.1-25.0% and 30.8%). Serious AEs were reported for 2.8-8.3% of patients in the deutetrabenazine groups and 6.9% in the placebo group. Common AEs (≥ 4%) included headache, somnolence, nausea, anxiety, fatigue, dry mouth, and diarrhea. AE incidence was higher during the titration vs maintenance periods. For HD, AE incidence was numerically higher with deutetrabenazine (n = 84) vs placebo (n = 45; any AE, 64.3% vs 60.0%; treatment-related AE, 38.1% vs 26.7%); serious AEs were reported for similar proportions for the deutetrabenazine and placebo groups, 2.4% and 2.2%, respectively. Common AEs (≥ 4%) included irritability, fall, depression, dry mouth, and fatigue.
Conclusions: Data from an integrated analysis of studies in TD and an integrated analysis of studies of chorea in HD showed that deutetrabenazine has a favorable safety profile and is well tolerated across indications.
Trial Registration: ClinicalTrials.gov identifiers, NCT02291861, NCT02195700, NCT01795859, NCT02198794, NCT01897896.
(© 2024. The Author(s).)
Databáze: MEDLINE
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