Session Information
Date: Wednesday, June 22, 2016
Session Title: Huntington's disease
Session Time: 12:00pm-1:30pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: To compare the tolerability of deutetrabenazine (DTB) and tetrabenazine (TBZ) as observed in the FIRST-HD (NCT01795859) and TETRA-HD (NCT00219804) trials for the treatment of chorea associated with Huntington’s disease (HD).
Background: DTB is a novel, selective vesicular monoamine transporter 2 inhibitor that contains deuterium, a naturally occurring, nontoxic form of hydrogen that extends active metabolite half-lives and minimizes drug concentration fluctuations. TBZ and DTB have not been compared in a head-to-head clinical trial.
Methods: Aggregate data from the 12-week, parallel-group, phase 3 clinical trials FIRST-HD (N=90) and TETRA-HD (N=84) were used to conduct an indirect comparison of the safety of DTB vs TBZ using the Bucher method, an accepted analytical approach. Serious adverse events (SAEs), discontinuation (all-cause and AE-related), and specific AEs that occurred in >10% of patients were included in the analysis. Placebo-adjusted risk differences in these outcomes were computed (difference of observed rate between the active and placebo arm) in each trial. The risk differences of these outcomes for DTB vs TBZ were estimated by subtracting the applicable placebo-adjusted risk in the TETRA-HD trial from the FIRST-HD trial. P values were obtained from z-tests.
Results: The trials were similar in design. For patients in FIRST-HD and TETRA-HD trials, respectively, mean age was 53.8 (both trials), mean baseline chorea scores were 12.7 and 14.9, and percentage of female participants was 44% and 62%. Among the safety outcomes, DTB had a statistically significant lower risk of drowsiness/somnolence (P=0.02), insomnia (P<0.01), and agitation (P=0.02) compared with TBZ.
Conclusions: In this indirect comparison, DTB demonstrated statistically significantly better tolerability than TBZ on several safety and tolerability outcomes. Further analysis adjusting for demographic differences between trials should be conducted to confirm these findings.
To cite this abstract in AMA style:
D.O. Claassen, B. Carroll, L.M. De Boer, E. Wu, R. Ayyagari, S. Gandhi, D. Stamler. Indirect comparison of tolerability of deutetrabenazine and tetrabenazine in the FIRST-HD and TETRA-HD trials [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/indirect-comparison-of-tolerability-of-deutetrabenazine-and-tetrabenazine-in-the-first-hd-and-tetra-hd-trials/. Accessed September 27, 2023.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/indirect-comparison-of-tolerability-of-deutetrabenazine-and-tetrabenazine-in-the-first-hd-and-tetra-hd-trials/