Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia

Hubert H. Fernandez, David Stamler, Mat D. Davis, Stewart A. Factor, Robert A. Hauser, Joohi Jimenez-Shahed, William G. Ondo, L. Fredrik Jarskog, Scott W. Woods, Danny Bega, Mark S. Ledoux, David R. Shprecher, Karen E. Anderson

Research output: Contribution to journalArticle

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 â Much Improved' or â 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.

Original languageEnglish (US)
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
StatePublished - Jan 1 2019

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Safety
Psychomotor Agitation
Cytochrome P-450 CYP2D6
deutetrabenazine
Tardive Dyskinesia
Incidence
Dyskinesias
Parkinsonian Disorders
Ambulatory Care
Anxiety
Placebos
Research Personnel
Depression
Therapeutics
Abnormal Involuntary Movement Scale

All Science Journal Classification (ASJC) codes

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

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. https://doi.org/10.1136/jnnp-2018-319918

Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. / Fernandez, Hubert H.; Stamler, David; Davis, Mat D.; Factor, Stewart A.; Hauser, Robert A.; Jimenez-Shahed, Joohi; Ondo, William G.; Jarskog, L. Fredrik; Woods, Scott W.; Bega, Danny; Ledoux, Mark S.; Shprecher, David R.; Anderson, Karen E.

In: Journal of Neurology, Neurosurgery and Psychiatry, 01.01.2019.

Research output: Contribution to journalArticle

Fernandez, HH, Stamler, D, Davis, MD, Factor, SA, Hauser, RA, Jimenez-Shahed, J, Ondo, WG, Jarskog, LF, Woods, SW, Bega, D, Ledoux, MS, Shprecher, DR & Anderson, KE 2019, 'Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia', Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2018-319918
Fernandez, Hubert H. ; Stamler, David ; Davis, Mat D. ; Factor, Stewart A. ; Hauser, Robert A. ; Jimenez-Shahed, Joohi ; Ondo, William G. ; Jarskog, L. Fredrik ; Woods, Scott W. ; Bega, Danny ; Ledoux, Mark S. ; Shprecher, David R. ; Anderson, Karen E. / Long-term safety and efficacy of deutetrabenazine for the treatment of tardive dyskinesia. In: Journal of Neurology, Neurosurgery and Psychiatry. 2019.
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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.

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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 â Much Improved' or â 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.

AB - 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 â Much Improved' or â 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.

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