Abstract
BACKGROUND: Tourette syndrome (TS) is a chronic neurodevelopmental tic disorder with a considerable quality of life (QOL) burden. OBJECTIVES: The goal was to determine the long-term safety, tolerability, and clinical effects of ecopipam, a first-in-class dopamine D1 receptor antagonist, for TS. METHODS: This 12-month, open-label extension (OLE) study enrolled patients age ≥6 to ≤18 years with confirmed TS who completed a phase 2b randomized, placebo-controlled, 12-week trial. Ecopipam was titrated over 4 weeks to achieve a target oral dose of 1.8 mg/kg/day. Study visits occurred at baseline, monthly for 12 months, and 7 and 14 days after last dose. RESULTS: A total of 121 patients were included (74% male; 68% age 12-18 years), and 80 (66%) completed the study. Ecopipam was well tolerated. The most common adverse events were nasopharyngitis (14.0%) and anxiety (9.1%). At month 12, there were no significant changes from baseline in body mass index Z-score (mean [standard deviation] change, 0.05 [0.43]; P = 0.35), glycated hemoglobin (0.03% [0.31]; P = 0.60), or total cholesterol (0.2 mmol/L [0.7]; P = 0.14). No notable changes in scales assessing akathisia, movement disorders, anxiety, or depression occurred. At all time points, significant improvements (P < 0.001 vs. baseline) in both the Yale Global Tic Severity Scale Total Tic Score and the Gilles de la Tourette Syndrome Quality of Life Scale for Children and Adolescents total score were observed. CONCLUSIONS: Twelve months of ecopipam dosing was well tolerated during this study and no new adverse events were detected. Compared to baseline, significantly reduced TS symptom severity and improved QOL were observed in children and adolescents.