Efficacy and Safety of Ecopipam for Tourette Syndrome: Results from a Phase 3, Double-blind, Placebo-controlled, Randomized Withdrawal Trial
Kinga Tomczak1, Sarah Atkinson2, David Kim2, Meredith Miller2, Patricia Rice2, George Karkanias2, Frederick Munschauer2, Stephen Wanaski3, Timothy Cunniff3, Donald Gilbert4
1Boston Children's Hospital Tic Disorders and Tourette Syndrome Program, 2Emalex Biosciences, 3Paragon Biosciences, 4University of Cincinnati College of Medicine
Objective:
To evaluate the efficacy/safety of ecopipam, a selective dopamine D1 receptor antagonist, as a maintenance therapy in children/adolescents/adults with Tourette syndrome (TS).
Background:
Current TS pharmacotherapies are limited by the risk of adverse events (AEs; eg, weight gain, metabolic abnormalities, drug-induced movement disorders). A pediatric phase 2b trial showed ecopipam significantly reduced TS tics versus placebo with limited occurrence of some of the complications reported with use of current pharmacotherapies.
Design/Methods:
Patients aged ≥6 y with TS were included in a double-blind, placebo-controlled, randomized withdrawal trial. Ecopipam was titrated over 3 to 4 weeks (target dose, 1.8 mg/kg/day) in the 12-week open-label period. Patients with a clinically meaningful reduction (≥25%) in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) at Weeks 8 and 12 were randomized to continue ecopipam or taper to placebo in the 12-week double-blind period. Time to relapse (≥50% loss of open-label YGTSS-TTS improvement) was determined in participants aged 6 to <18 years (primary efficacy endpoint) and all participants (secondary endpoint) during the withdrawal period.
Results:
216 patients were enrolled in the 12-week open-label phase. Overall, 104 patients (90 pediatric) were randomized to the 12-week double-blind period to continue ecopipam (n=51; 84.3% pediatric, 72.5% male) or switch to placebo (n=53; 88.7% pediatric, 66.0% male). The risk of relapse was significantly reduced in the ecopipam group compared with placebo in 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 commonly reported AEs (≥5.0%), regardless of causality, in the ecopipam group during the 24-week study were somnolence (11.1%), anxiety (9.7%), headache (9.7%), insomnia (8.8%), tic (7.9%), and fatigue (6.5%).
Conclusions:
This study demonstrated that ecopipam maintained clinically meaningful improvements in TS symptoms; was generally well-tolerated, with AEs primarily affecting the CNS; and did not cause weight gain, dyslipidemia, or drug-induced movement disorders.
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