Objective: To determine the efficacy and safety of deutetrabenazine (DTB) as a treatment for tardive dyskinesia (TD).

Background: There is no approved treatment for TD, a common, often irreversible movement disorder caused by chronic exposure to dopamine receptor antagonists. VMAT2 inhibition is a potential treatment approach. DTB is a novel, selective VMAT2 inhibitor that contains deuterium, a naturally occurring, nontoxic form of hydrogen that extends active metabolite half-lives and minimizes drug concentration fluctuations.

Methods: Patients with moderate to severe TD were randomized 1:1 to DTB or placebo in this double-blind, parallel-group study. Dose was titrated over 6 weeks and then maintained for 6 weeks. Key inclusion criteria included an Abnormal Involuntary Movement Scale (AIMS) score ≥6, stable psychiatric illness (if present), and stable dosing of current medications. The primary endpoint was change in AIMS score from baseline (BL) to Week 12 as assessed by blinded movement disorder central video raters. The key secondary endpoint was the proportion of patients experiencing treatment success (“much” or “very much” improved) at Week 12 on the Clinical Global Impression of Change (CGIC).

Results: 117 patients from 46 sites received DTB (n=58) or placebo (n=59). DTB significantly reduced mean AIMS scores compared with placebo at Week 12 (3.0 vs 1.6; P=.019). On the CGIC, 48.2% of DTB patients experienced treatment success vs 40.4% for placebo (P=.40). In patients with central video AIMS ratings ≥6 at both screening and BL (n=97), mean AIMS scores decreased by 3.5 in the DTB group vs 1.8 for placebo (P=.017), and on the CGIC, treatment success was reported by 52.1% vs 34.7% of patients at Week 12 (P=.084). Treatment-emergent AEs were reported in 70.7% and 61% of DTB and placebo groups, respectively. The most common AEs reported were somnolence (n=8 [13.8%] vs n=6 [10.2%]) and headache (n=4 [6.9%] vs n=6 [10.2%]) in the DTB and placebo groups, respectively. Both groups had low rates of psychiatric AEs, such as psychosis (n=1 [1.7%] DTB vs n=0 placebo) and suicidal ideation (n=0 DTB vs n=1 [1.7%] placebo). One (1.7%) DTB patient withdrew due to AEs vs 2 (3.4%) in the placebo group.

Conclusions: DTB significantly reduced abnormal involuntary movements and was well tolerated with a favorable safety profile and low withdrawal rate.

American Psychiatric Association, May 14-18 2016.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-randomized-double-blind-placebo-controlled-trial-of-deutetrabenazine-for-the-treatment-of-tardive-dyskinesia-arm-td/