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TETRA-HD

Tetrabenazine as anti-chorea therapy in Huntington Disease: an open-label continuation study

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Year of Publication: 2009

Authors: Samuel Frank and the Huntington Study Group/TETRA-HD Investigators

Journal: BMC Neurology

Citation: BMC Neurology 2009;9:62

Link: https://doi.org/10.1186/1471-2377-9-62

PDF: https://vertexaisearch.cloud.google.com/...UM2UjvxOLjWvE0=

Clinical Question

Does tetrabenazine safely and effectively suppress chorea in HD over long-term treatment?

Bottom Line

Deutetrabenazine significantly reduced chorea in Huntington disease vs placebo: UHDRS Total Maximal Chorea score improved -2.5 vs -0.1 (P<0.001). Well tolerated with less adverse effects than tetrabenazine. Published JAMA 2016. Led to FDA approval.

        Major Points
        UHDRS Total Maximal Chorea: -2.5 (deutetrabenazine) vs -0.1 (placebo); P<0.001.
90 HD patients with chorea. 12-week, double-blind, placebo-controlled.
Dose: deutetrabenazine 12-48 mg/day (titrated based on response and tolerability).
Patient Global Impression of Change: 51% improved vs 20% placebo (P=0.002).
Better tolerated than tetrabenazine: no increased depression, somnolence, or akathisia vs placebo.
Deutetrabenazine: deuterated form of tetrabenazine — longer half-life, lower Cmax, BID dosing.
AEs: somnolence (11% vs 4%), diarrhea (9% vs 0%), dry mouth. Depression not increased.
Published JAMA 2016 (Huntington Study Group). Teva sponsored. FDA approved 2017.
VMAT2 inhibitor — reduces dopamine release to suppress chorea.
Advantage over tetrabenazine: fewer neuropsychiatric side effects, BID vs TID dosing.

      

Design

Study Type: Open-label extension study

Blinding: Open-label

Sample Size: 75

Centers: Multicenter (HSG sites)

Follow-up Duration: 80 weeks + 1-week washout

Inclusion Criteria

Completed 13-week double-blind TETRA-HD trial
Enrolled within 8 weeks of completing double-blind study

Exclusion Criteria

Serious AE related to study drug in double-blind phase
Use of prohibited medications

Arms

Field	Tetrabenazine
Intervention	Tetrabenazine 12.5–200 mg/day titrated to best individual dose, oral
Duration	80 weeks

Outcomes

Outcome	Type	Control	Intervention	P-value
TMC score at week 80	Primary	Baseline TMC	-4.6 units improvement	<0.001
CGI	Secondary	Improved 0.3 points, P=0.0054
Parkinsonism	Secondary	Increased 2.1 units, P=0.002

Criticisms

Open-label design
40% attrition
No comparison group
Depression monitoring limited

Funding

Prestwick Pharmaceuticals (Biovail)

Based on: TETRA-HD (BMC Neurology, 2009)