Abstract Details

Title Evaluation of the Safety of Deutetrabenazine at Higher Doses to Treat Chorea in Huntington’s Disease

Topic Movement Disorders

Presentation(s) P5 - Poster Session 5 (8:00 AM-9:00 AM)

Poster/Presentation
Number 3-017

Objective To evaluate the safety and tolerability of deutetrabenazine >48 mg/d compared to ≤48 mg/d to treat Huntington’s disease (HD)–associated chorea in ARC-HD.

Background

In the First-HD pivotal trial, the maximum deutetrabenazine dose evaluated to treat HD chorea was 48 mg/d, which is the approved maximum dose for this population. In ARC-HD, an open-label extension study evaluating the long-term efficacy and safety of deutetrabenazine to treat HD chorea, dosage ranged from 6 mg/d to 72 mg/d. Doses in ARC-HD were increased by 6 mg/d per week in a response-driven manner based on efficacy and tolerability until 48 mg/d (week 8), and, at investigator’s discretion, further increases were permitted by 12 mg/d per week to a maximum of 36 mg twice daily.

Design/Methods In this post-hoc analysis, patient counts and safety assessments were attributed to patients when they received a dose either ≤48 mg/d or >48 mg/d. For 9 selected adverse events (AEs), we compared AE rates adjusted for duration of drug exposure (as number of AEs/year) at ≤48 mg/d or >48 mg/d. The AE rates were determined after titration when participants were on stable doses of deutetrabenazine.

Results All 113 patients were exposed to doses ≤48 mg/d (177.1 patient-years), but only 49 subjects were ever exposed to doses >48 mg/d (74.1 patient-years). In patients taking deutetrabenazine >48 mg/d compared to ≤48 mg/d after the titration period, there were no apparent differences in exposure-adjusted AE rates.

Conclusions Some patients with HD require doses higher than 48 mg/day to adequately control chorea. These doses were tolerated without apparent increase in the exposure-adjusted rates of selected AEs after titration. This analysis does not address the occurrence of other AEs or whether adequate efficacy was achieved at lower doses, factors that may have influenced dose increases.

Authors/Disclosures
Samuel A. Frank, MD, F�鶹��ýӳ�� (Beth Israel Deaconess Medical Center/Harvard Medical School) PRESENTER	Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for uniQure. Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva. Dr. Frank has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. The institution of Dr. Frank has received research support from Huntington's Disease Society of America. The institution of Dr. Frank has received research support from Roche/Genentech. The institution of Dr. Frank has received research support from CHDI Foundation. The institution of Dr. Frank has received research support from Huntington Study Group. The institution of Dr. Frank has received research support from Cerevel.
Christina L. Vaughan, MD, MHS (University of Colorado, School of Medicine)	Dr. Vaughan has nothing to disclose.
David A. Stamler, MD (Alterity Therapeutics)	Dr. Stamler has received personal compensation for serving as an employee of Alterity Therapeutics. Dr. Stamler has stock in Alterity Therapeutics.
	No disclosure on file
Mat D. Davis	Mat D. Davis has received personal compensation for serving as an employee of Teva pharmaceuticals. Mat D. Davis has received stock or an ownership interest from Teva Pharmaceuticals.
	No disclosure on file
Mark F. Gordon, MD, F�鶹��ýӳ�� (Teva Pharmaceuticals)	Dr. Gordon has received personal compensation for serving as an employee of Teva. Dr. Gordon has stock in Teva.
	No disclosure on file
Maria Wieman, MPH	No disclosure on file
	No disclosure on file
Elise P. Kayson, RN	Elise Paulin Kayson, RN has nothing to disclose.
	No disclosure on file
	No disclosure on file
Claudia Testa, MD, PhD (University of North Carolina at Chapel Hill)	Dr. Testa has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neurocrine. Dr. Testa has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for uniQure. Dr. Testa has received personal compensation in the range of $5,000-$9,999 for serving as an officer or member of the Board of Directors for Tremor Research Group.

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