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Multicenter Study
. 2017 Aug 1;74(8):977-982.
doi: 10.1001/jamaneurol.2017.1352.

Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea

Samuel Frank  1 , David Stamler  2 , Elise Kayson  3 , Daniel O Claassen  4 , Amy Colcher  5 , Charles Davis  6 , Andrew Duker  7 , Shirley Eberly  3 , Lawrence Elmer  8 , Erin Furr-Stimming  9 , Mark Gudesblatt  10 , Christine Hunter  11 , Joseph Jankovic  11 , Sandra K Kostyk  12 , Rajeev Kumar  13 , Clement Loy  14 , William Mallonee  15 , David Oakes  16 , Burton L Scott  17 , Victor Sung  18 , Jody Goldstein  3 , Christina Vaughan  19 , Claudia M Testa  20 ; Huntington Study Group/Alternatives for Reducing Chorea in Huntington Disease Investigators
Affiliations
Multicenter Study

Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea

Samuel Frank et al. JAMA Neurol. .

Erratum in

  • Incorrect Affiliation.
    [No authors listed] [No authors listed] JAMA Neurol. 2018 Jan 1;75(1):133. doi: 10.1001/jamaneurol.2017.3563. JAMA Neurol. 2018. PMID: 29131881 Free PMC article. No abstract available.

Abstract

Importance: Tetrabenazine is efficacious for chorea control; however, tolerability concerns exist. Deutetrabenazine, a novel molecule that reduces chorea, was well tolerated in a double-blind, placebo-controlled study.

Objectives: To evaluate the safety and explore the efficacy of conversion from tetrabenazine to deutetrabenazine in patients with chorea associated with Huntington disease (HD).

Design, setting, and participants: In this ongoing, open-label, single-arm study that started on December 21, 2013, 37 patients at 13 Huntington Study Group sites in the United States and Australia who were taking stable doses of tetrabenazine that provided a therapeutic benefit were switched overnight to deutetrabenazine therapy. After week 1, the deutetrabenazine dose was titrated on a weekly basis for optimal chorea control.

Interventions: Deutetrabenazine administration at a dosage thought to provide comparable systemic exposure to the active metabolites of the prior, stable tetrabenazine regimen.

Main outcomes and measures: Safety measures included adverse events (AEs), clinical laboratory tests, vital signs, electrocardiograms, and validated scales. Changes in the Unified Huntington's Disease Rating Scale total maximal chorea score and total motor score were efficacy end points.

Results: Of the 53 patients with HD screened for the study, 37 ambulatory patients with manifest HD (mean [SD] age, 52.4 [11.5] years; 22 [59%] male and 15 [41%] female; 36 white [97.3%]) were enrolled. Deutetrabenazine was generally well tolerated, with low rates of neuropsychiatric AEs. Safety scales did not reveal subclinical toxicity with deutetrabenazine treatment. Rates of dose reduction or suspension attributable to AEs were also low. Chorea control, as measured by the total maximal chorea score, was maintained at week 1 and significantly improved at week 8 (mean [SD] change from baseline, 2.1 [3.2]; P < .001).

Conclusions and relevance: In patients with chorea, overnight conversion to deutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Frank reported receiving grants from the Huntington Study Group. Dr Stamler reported being an employee of Auspex Pharmaceuticals. Ms Kayson reported receiving honoraria and funding for a meeting from Raptor Pharmaceutical and serving as a consultant to Pfizer Inc. Dr Davis reported serving as a consultant for Auspex Pharmaceuticals. Dr Duker reported receiving grants and nonfinancial support from HSG on behalf of Auspex Pharmaceuticals during the conduct of the study and other support from Auspex Pharmaceuticals outside the submitted work. Dr Furr-Stimming reported serving as a consultant for Cynapsus and on the speakers’ bureau for Lundbeck (Xenazine) and Teva (Azilect). Dr Jankovic reported receiving research and/or training grants from Adamas Pharmaceuticals Inc, Allergan Inc, CHDI Foundation, Civitas/Acorda Therapeutics, Dystonia Medical Research Foundation, Huntington Study Group, Ipsen Limited, Kyowa Haako Kirin Pharma Inc, Lundbeck Inc, Medtronic, Merz Pharmaceuticals, Michael J. Fox Foundation for Parkinson Research, National Institutes of Health, National Parkinson Foundation, Parkinson Study Group, Pfizer, Prothena Biosciences Inc, Psyadon Pharmaceuticals Inc, St. Jude Medical, and Teva Pharmaceutical Industries Ltd. Dr Jankovic reported serving as a consultant or as an advisory committee member for Adamas Pharmaceuticals Inc, Allergan Inc, and Teva Pharmaceutical Industries Ltd. Dr Jankovic reported receiving royalties from Cambridge, Elsevier, Future Science Group, Hodder Arnold, Lippincott Williams and Wilkins, and Wiley-Blackwell and serving on editorial boards for Medlink Neurology, Expert Review of Neurotherapeutics, Neurology in Clinical Practice, The Botulinum Journal, PeerJ, Therapeutic Advances in Neurological Disorders, Neurotherapeutics, Tremor and Other Hyperkinetic Movements, Journal of Parkinson's Disease, and UpToDate. Dr Kostyk reported receiving consultant fees from the National Institutes of Health and the US Food and Drug Administration and has had meeting travel costs covered through the Huntington's Study Group and Pfizer Pharmaceuticals. Dr Kumar reported receiving personal fees from Teva Pharmaceuticals outside the submitted work. Dr Mallonee reported receiving other support from HSG on behalf of Auspex Pharmaceuticals during the conduct of the study. Dr Oakes reported receiving research support from Auspex for this and another study of SD809 in Huntington disease (HD), Vaccinex Inc and Prana Pharmaceuticals for studies in HD, Biogen Inc for a study in Parkinson disease, and the National Institutes of Health for studies in HD and Parkinson disease and personal honoraria from Raptor Pharmaceuticals and Voyager Inc. Dr Sung reported receiving personal fees from Lundbeck Inc. Dr Testa reported receiving grants from the Huntington Study Group, Teva Pharmaceuticals, and the CHDI Foundation and other support from Auspex Pharmaceuticals and Lundbeck Pharmaceuticals outside the submitted work. No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Flow of Study Patients
After screening for eligibility, a total of 37 patients were enrolled. Of the 37 patients, 1 patient withdrew and all others continued in the ongoing study.
Figure 2.
Figure 2.. Mean Change in Total Maximal Chorea (TMC) Score
The TMC score was assessed during 8 weeks. The TMC assessments at baseline (blue dotted line) and weeks 1, 4, and 8 are represented for the median daily doses of deutetrabenazine. Error bars represent SEM. aP < .001.
Figure 3.
Figure 3.. Mean Change in Total Motor Score (TMS) After Switch
The TMS was evaluated during 8 weeks. The TMS assessments at baseline (blue dotted line) and weeks 1, 4, and 8 are represented for the median daily doses of deutetrabenazine. Error bars represent SEM. aP = .02.
See this image and copyright information in PMC

References

    1. Burgunder J-M, Guttman M, Perlman S, Goodman N, van Kammen DP, Goodman L. An international survey-based algorithm for the pharmacological treatment of chorea in Huntington’s disease. PLoS Curr. 2011;3:RRN1260. - PMC - PubMed
    1. Jankovic J, Roos RA. Chorea associated with Huntington’s disease: to treat or not to treat? Mov Disord. 2014;29(11):1414-1418. - PubMed
    1. Kenney C, Hunter C, Jankovic J. Long-term tolerability of tetrabenazine in the treatment of hyperkinetic movement disorders. Mov Disord. 2007;22(2):193-197. - PubMed
    1. Jankovic J. Dopamine depleters in the treatment of hyperkinetic movement disorders. Expert Opin Pharmacother. 2016;17(18):2461-2470. - PubMed
    1. AustedoTM [package insert]. North Wales, PA: Teva Pharmaceuticals Inc; 2017.

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