PMID- 28692723 OWN - NLM STAT- MEDLINE DCOM- 20170822 LR - 20200306 IS - 2168-6157 (Electronic) IS - 2168-6149 (Print) IS - 2168-6149 (Linking) VI - 74 IP - 8 DP - 2017 Aug 1 TI - Safety of Converting From Tetrabenazine to Deutetrabenazine for the Treatment of Chorea. PG - 977-982 LID - 10.1001/jamaneurol.2017.1352 [doi] AB - 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. FAU - Frank, Samuel AU - Frank S AD - Department of Neurology, Harvard Medical School, Boston, Massachusetts. FAU - Stamler, David AU - Stamler D AD - Teva Pharmaceutical Industries, Frazer, Pennsylvania. FAU - Kayson, Elise AU - Kayson E AD - Clinical Trials Coordination Center, University of Rochester, Rochester, New York. FAU - Claassen, Daniel O AU - Claassen DO AD - Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. FAU - Colcher, Amy AU - Colcher A AD - Department of Neurology, Cooper University Hospital, Camden, New Jersey. FAU - Davis, Charles AU - Davis C AD - CSD Biostatistics, Tucson, Arizona. FAU - Duker, Andrew AU - Duker A AD - Department of Neurology, University of Cincinnati, Cincinnati, Ohio. FAU - Eberly, Shirley AU - Eberly S AD - Clinical Trials Coordination Center, University of Rochester, Rochester, New York. FAU - Elmer, Lawrence AU - Elmer L AD - The Center for Neurologic Health, Toledo, Ohio. FAU - Furr-Stimming, Erin AU - Furr-Stimming E AD - Department of Neurology, The University of Texas Medical School, Houston. FAU - Gudesblatt, Mark AU - Gudesblatt M AD - South Shore Neurologic Associates, Islip, New York. FAU - Hunter, Christine AU - Hunter C AD - Department of Neurology, Baylor College of Medicine, Houston, Texas. FAU - Jankovic, Joseph AU - Jankovic J AD - Department of Neurology, Baylor College of Medicine, Houston, Texas. FAU - Kostyk, Sandra K AU - Kostyk SK AD - Department of Neurology, The Ohio State University, Columbus. FAU - Kumar, Rajeev AU - Kumar R AD - Rocky Mountain Movement Disorders Center, Englewood, Colorado. FAU - Loy, Clement AU - Loy C AD - Department of Neurology, University of Sydney, Sydney, Australia. FAU - Mallonee, William AU - Mallonee W AD - Hereditary Neurological Disease Centre, Wichita, Kansas. FAU - Oakes, David AU - Oakes D AD - Department of Statistics, University of Rochester, Rochester, New York. FAU - Scott, Burton L AU - Scott BL AD - Department of Neurology, Duke University, Durham, North Carolina. FAU - Sung, Victor AU - Sung V AD - Department of Neurology, University of Alabama School of Medicine, Birmingham. FAU - Goldstein, Jody AU - Goldstein J AD - Clinical Trials Coordination Center, University of Rochester, Rochester, New York. FAU - Vaughan, Christina AU - Vaughan C AD - Department of Neurology, Medical University of South Carolina, Charleston. FAU - Testa, Claudia M AU - Testa CM AD - Department of Neurology, Virginia Commonwealth University, Richmond. CN - Huntington Study Group/Alternatives for Reducing Chorea in Huntington Disease Investigators LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Neurol JT - JAMA neurology JID - 101589536 RN - 0 (Adrenergic Uptake Inhibitors) RN - P341G6W9NB (deutetrabenazine) RN - Z9O08YRN8O (Tetrabenazine) SB - IM EIN - JAMA Neurol. 2018 Jan 1;75(1):133. PMID: 29131881 MH - Adrenergic Uptake Inhibitors/*therapeutic use MH - Australia MH - Chorea/*drug therapy MH - Drug Substitution/*methods MH - Female MH - Follow-Up Studies MH - Humans MH - Male MH - Middle Aged MH - Severity of Illness Index MH - Tetrabenazine/*analogs & derivatives/*therapeutic use MH - Treatment Outcome MH - United States PMC - PMC5710322 COIS- 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. EDAT- 2017/07/12 06:00 MHDA- 2017/08/23 06:00 PMCR- 2018/07/10 CRDT- 2017/07/11 06:00 PHST- 2017/07/12 06:00 [pubmed] PHST- 2017/08/23 06:00 [medline] PHST- 2017/07/11 06:00 [entrez] PHST- 2018/07/10 00:00 [pmc-release] AID - 2643174 [pii] AID - noi170038 [pii] AID - 10.1001/jamaneurol.2017.1352 [doi] PST - ppublish SO - JAMA Neurol. 2017 Aug 1;74(8):977-982. doi: 10.1001/jamaneurol.2017.1352.