(62) Efficacy and safety of ecopipam for Tourette syndrome: results from a phase 3, randomized, double-blind, placebo-controlled withdrawal trial

Background: : Current pharmacotherapies for Tourette syndrome (TS) are limited by the risk for weight gain, metabolic abnormalities, and drug-induced movement disorders. A previous pediatric phase 2b trial showed ecopipam significantly reduced TS tics versus placebo, with no difference from placebo in weight gain, metabolic changes, or abnormal involuntary movements.

Objective: : The objective of this phase 3 trial was to evaluate the durability of efficacy and safety of ecopipam, an investigational dopamine D1 receptor antagonist, in TS.

Methods: : In participants with TS who were at least 6 years of age, ecopipam was titrated over 4 weeks (target dose, 1.8 mg/kg/day) during a 12-week, open-label period. Individuals with at least a 25% reduction in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at both Weeks 8 and 12 were randomized to continue on ecopipam or taper to placebo during a 12-week double-blind period. The primary efficacy endpoint was time to relapse. Relapse was defined as at least a 50% loss of improvement in the YGTSS-TTS previously observed from baseline to Week 12 in the pediatric cohort (aged 6 to less than 18 years).

Results: : A total of 216 participants (167 pediatric patients; 49 adults) were enrolled in the open-label period. Of these, 104 (90 pediatric patients; 14 adults) were randomly assigned to continue ecopipam (n=51; 84.3% pediatric) or down-titrate to placebo (n=53; 88.7% pediatric). The risk of relapse was significantly reduced in the ecopipam group compared to placebo in both the pediatric (hazard ratio [HR]=0.5 [0.3, 0.8]; P=0.008) and pediatric plus adult (HR=0.5 [0.3, 0.8]; P=0.005) populations. The most common treatment-related adverse events with ecopipam were somnolence (10.2%), insomnia (7.4%), anxiety (6.0%), fatigue (5.6%), and headache (5.1%).

Conclusions: : This study demonstrated that ecopipam maintained clinically meaningful improvements in TS symptoms, was generally well tolerated, and did not cause weight gain, dyslipidemia, or drug-induced movement disorders.

Sponsorship:: Emalex Biosciences, Inc.