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Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia.
J Neurol Neurosurg Psychiatry 2019; 90(12):1317-1323JN

Abstract

OBJECTIVE

To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD).

METHOD

Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change.

RESULTS

A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8).

CONCLUSIONS

Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD.

TRIAL REGISTRATION NUMBER

NCT02198794.

Authors+Show Affiliations

Center for Neurological Restoration, Cleveland Clinic Foundation, Cleveland, Ohio, USA fernanh@ccf.org.Former employee of Teva Pharmaceuticals, La Jolla, California, USA.Teva Pharmaceuticals, Frazer, Pennsylvania, USA.Jean and Paul Amos Parkinson's Disease and Movement Disorder Program, Emory University School of Medicine, Atlanta, Georgia, USA.University of South Florida Parkinson's Disease and Movement Disorders Center, Tampa, Florida, USA.Baylor College of Medicine, Houston, Texas, USA.Methodist Neurological Institute, Houston, Texas, USA. Weill Cornell Medical College, New York, New York, USA.University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA.Yale University School of Medicine, New Haven, Connecticut, USA.Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.University of Tennessee Health Science Center, Memphis, Tennessee, USA.University of Utah, Salt Lake City, Utah, USA. Banner Sun Health Research Institute, Sun City, Arizona, USA.Georgetown University, Washington, District of Columbia, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31296586

Citation

Fernandez, Hubert H., et al. "Long-term Safety and Efficacy of Deutetrabenazine for the Treatment of Tardive Dyskinesia." Journal of Neurology, Neurosurgery, and Psychiatry, vol. 90, no. 12, 2019, pp. 1317-1323.
Fernandez HH, Stamler D, Davis MD, et al. Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. J Neurol Neurosurg Psychiatry. 2019;90(12):1317-1323.
Fernandez, H. H., Stamler, D., Davis, M. D., Factor, S. A., Hauser, R. A., Jimenez-Shahed, J., ... Anderson, K. E. (2019). Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. Journal of Neurology, Neurosurgery, and Psychiatry, 90(12), pp. 1317-1323. doi:10.1136/jnnp-2018-319918.
Fernandez HH, et al. Long-term Safety and Efficacy of Deutetrabenazine for the Treatment of Tardive Dyskinesia. J Neurol Neurosurg Psychiatry. 2019;90(12):1317-1323. PubMed PMID: 31296586.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. AU - Fernandez,Hubert H, AU - Stamler,David, AU - Davis,Mat D, AU - Factor,Stewart A, AU - Hauser,Robert A, AU - Jimenez-Shahed,Joohi, AU - Ondo,William G, AU - Jarskog,L Fredrik, AU - Woods,Scott W, AU - Bega,Danny, AU - LeDoux,Mark S, AU - Shprecher,David R, AU - Anderson,Karen E, Y1 - 2019/07/10/ PY - 2018/10/30/received PY - 2019/05/21/revised PY - 2019/06/18/accepted PY - 2019/7/13/pubmed PY - 2019/7/13/medline PY - 2019/7/13/entrez KW - deutetrabenazine KW - movement disorders KW - tardive dyskinesia KW - vmat2 inhibitor SP - 1317 EP - 1323 JF - Journal of neurology, neurosurgery, and psychiatry JO - J. Neurol. Neurosurg. Psychiatry VL - 90 IS - 12 N2 - OBJECTIVE: To evaluate the long-term safety and efficacy of deutetrabenazine in patients with tardive dyskinesia (TD). METHOD: Patients with TD who completed the 12 week, phase 3, placebo-controlled trials were eligible to enter this open-label, single-arm study. The open-label study consisted of a 6 week dose-escalation phase and a long-term maintenance phase (clinic visits at Weeks 4, 6 and 15, and every 13 weeks until Week 106). Patients began deutetrabenazine at 12 mg/day, titrating up to a dose that was tolerable and provided adequate dyskinesia control, based on investigator judgement, with a maximum allowed dose of 48 mg/day (36 mg/day for patients taking strong cytochrome P450 2D6 (CYP2D6) inhibitors). Safety measures included incidence of adverse events (AEs) and scales used to monitor parkinsonism, akathisia/restlessness, anxiety, depression, suicidality and somnolence/sedation. Efficacy endpoints included the change in Abnormal Involuntary Movement Scale (AIMS) score (items 1 to 7) from baseline and the proportion of patients rated as 'Much Improved' or 'Very Much Improved' on the Clinical Global Impression of Change. RESULTS: A total of 343 patients enrolled in the extension study, and there were 331 patient-years of exposure in this analysis. The exposure-adjusted incidence rates of AEs with long-term treatment were comparable to or lower than those observed in the phase 3 trials. The mean (SE) change in AIMS score was -4.9 (0.4) at Week 54 (n = 146), - 6.3 (0.7) at Week 80 (n = 66) and -5.1 (2.0) at Week 106 (n = 8). CONCLUSIONS: Overall, long-term treatment with deutetrabenazine was efficacious, safe, and well tolerated in patients with TD. TRIAL REGISTRATION NUMBER: NCT02198794. SN - 1468-330X UR - https://www.unboundmedicine.com/medline/citation/31296586/Long-term_safety_and_efficacy_of_deutetrabenazine_for_the_treatment_of_tardive_dyskinesia L2 - http://jnnp.bmj.com/cgi/pmidlookup?view=long&pmid=31296586 DB - PRIME DP - Unbound Medicine ER -