Abstract Details

Title First Time Use of SD-809 in Huntington Disease (First-HD)

Topic Movement Disorders

Presentation(s) (-)

Poster/Presentation
Number 012

Objective

Background SD-809 is a deuterated form of tetrabenazine, a VMAT-2 inhibitor used to treat hyperkinetic movement disorders including chorea, tics and tardive dyskinesia. Deuterium can alter metabolism of small molecule drugs without changing their pharmacology. SD-809 achieves comparable AUC to tetrabenazine, but with approximately half the dose and half the C_max.

Design/Methods This randomized, double-blind, placebo-controlled trial evaluated SD-809 in subjects with chorea. Study drug was titrated to adequate chorea control over 8 weeks, followed by 4-week maintenance and 1-week washout. Total daily dose ranged from 6-48 mg. Entry criteria included Total Maximal Chorea (TMC) score ?8, Total Functional Capacity score ?5 and no undertreated psychiatric illness.

Results 90 subjects (45:45) enrolled (44% female, mean age=53.7, mean CAGn=43.9). The TMC score on SD-809 improved by 2.5 points (21 percentage points) over placebo from baseline to maintenance therapy (p<0.0001).Total motor score (TMS) improved by 4.0 points over placebo (p=0.002). Significantly improved secondary endpoints included patient and clinical global impressions of change (each p=0.002) and SF-36 physical functioning scale (p=0.03). The mean SD-809 daily dose at end treatment was ~40 mg. Three subjects terminated early, 1 receiving SD-809. Adverse event (AE) rates were similar for SD-809 and placebo. Common AEs were irritability (SD-809: 6.7% vs. placebo: 13.3%), somnolence (11.1% vs. 4.4%), dry mouth (8.9% vs. 6.7%) and dizziness (4.4% vs. 8.9%). Depression, anxiety, akathisia and parkinsonism were reported at the same or lower frequency for SD-809 than placebo.

Conclusions SD-809 effectively reduced chorea in HD, with an impressive safety and tolerability profile with twice daily dosing. Treatment with SD-809 improved TMS beyond chorea and improved functional and quality of life measures, suggesting effective symptomatic treatment with good tolerability and overall benefit to HD patients.

Authors/Disclosures
Samuel A. Frank, MD, FAAN (Beth Israel Deaconess Medical Center/Harvard Medical School)	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.

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