Samuel Frank1, David Stamler2, Elise Kayson3, Daniel O Claassen4, Amy Colcher5, Charles Davis6, Andrew Duker7, Shirley Eberly3, Lawrence Elmer8, Erin Furr-Stimming9, Mark Gudesblatt10, Christine Hunter11, Joseph Jankovic11, Sandra K Kostyk12, Rajeev Kumar13, Clement Loy14, William Mallonee15, David Oakes16, Burton L Scott17, Victor Sung18, Jody Goldstein3, Christina Vaughan19, Claudia M Testa20. 1. Department of Neurology, Harvard Medical School, Boston, Massachusetts. 2. Teva Pharmaceutical Industries, Frazer, Pennsylvania. 3. Clinical Trials Coordination Center, University of Rochester, Rochester, New York. 4. Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee. 5. Department of Neurology, Cooper University Hospital, Camden, New Jersey. 6. CSD Biostatistics, Tucson, Arizona. 7. Department of Neurology, University of Cincinnati, Cincinnati, Ohio. 8. The Center for Neurologic Health, Toledo, Ohio. 9. Department of Neurology, The University of Texas Medical School, Houston. 10. South Shore Neurologic Associates, Islip, New York. 11. Department of Neurology, Baylor College of Medicine, Houston, Texas. 12. Department of Neurology, The Ohio State University, Columbus. 13. Rocky Mountain Movement Disorders Center, Englewood, Colorado. 14. Department of Neurology, University of Sydney, Sydney, Australia. 15. Hereditary Neurological Disease Centre, Wichita, Kansas. 16. Department of Statistics, University of Rochester, Rochester, New York. 17. Department of Neurology, Duke University, Durham, North Carolina. 18. Department of Neurology, University of Alabama School of Medicine, Birmingham. 19. Department of Neurology, Medical University of South Carolina, Charleston. 20. Department of Neurology, Virginia Commonwealth University, Richmond.
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 oftetrabenazine 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 todeutetrabenazine therapy provided a favorable safety profile and effectively maintained chorea control.
RCT Entities:
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.
Authors: Ziad S Nasreddine; Natalie A Phillips; Valérie Bédirian; Simon Charbonneau; Victor Whitehead; Isabelle Collin; Jeffrey L Cummings; Howard Chertkow Journal: J Am Geriatr Soc Date: 2005-04 Impact factor: 5.562
Authors: Kelly Posner; Gregory K Brown; Barbara Stanley; David A Brent; Kseniya V Yershova; Maria A Oquendo; Glenn W Currier; Glenn A Melvin; Laurence Greenhill; Sa Shen; J John Mann Journal: Am J Psychiatry Date: 2011-12 Impact factor: 18.112
Authors: A Feigin; K Kieburtz; K Bordwell; P Como; K Steinberg; J Sotack; C Zimmerman; C Hickey; C Orme; I Shoulson Journal: Mov Disord Date: 1995-03 Impact factor: 10.338
Authors: Samuel Frank; Claudia Testa; Mary C Edmondson; Jody Goldstein; Elise Kayson; Blair R Leavitt; David Oakes; Christine O'Neill; Christina Vaughan; Jacquelyn Whaley; Nicholas Gross; Mark Forrest Gordon; Juha-Matti Savola Journal: CNS Drugs Date: 2022-10-15 Impact factor: 6.497