PDF: TETRA-HD
(2009)Objective
To assess the long-term safety and effectiveness of tetrabenazine (TBZ) for chorea in Huntington disease
Study Summary
• Mean TMC score reduction of 4.6 units at week 80 (p<0.001), chorea re-emerged after washout
• 45/75 subjects (60%) completed 80 weeks; mean dosage 63.4 mg/day (range 12.5-175 mg)
• 45/75 subjects (60%) completed 80 weeks; mean dosage 63.4 mg/day (range 12.5-175 mg)
Intervention
Tetrabenazine (TBZ) 12.5-200 mg/day, titrated to best individual dose over 12 weeks
Inclusion Criteria
Completed prior 13-week double-blind TBZ trial, ambulatory HD patients with TFC >5 and TMC >9
Study Design
Arms: Single arm open-label extension
Patients per Arm: 75 enrolled, 45 completed 80 weeks
Outcome
• Primary: TBZ effectively suppressed chorea for up to 80 weeks (mean TMC reduction 4.6 units, p<0.001)
• Secondary: CGI improved 0.3 points (p=0.0054); parkinsonism and dysphagia scores increased; cognitive and functional decline consistent with natural HD progression
• Secondary: CGI improved 0.3 points (p=0.0054); parkinsonism and dysphagia scores increased; cognitive and functional decline consistent with natural HD progression
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.
Study Design
- Study Type
- Open-label extension study
- Blinding
- Open-label
- Sample Size
- 75
- Follow-up
- 80 weeks + 1-week washout
- Centers
- Multicenter (HSG sites)
Primary Outcome
Definition: TMC score at week 80
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| Baseline TMC | -4.6 units improvement | - | <0.001 |
Limitations & Criticisms
- Open-label design
- 40% attrition
- No comparison group
- Depression monitoring limited
Citation
BMC Neurology 2009;9:62