Objective: To assess the safety profile and effect of ecopipam, a selective dopamine D1 receptor antagonist, during the first 8 weeks of therapy for Tourette syndrome (TS) to help guide expectations during treatment initiation.

Background: TS is a childhood-onset neurodevelopmental disorder, and pharmacologic intervention is recommended when behavioral therapy is unavailable, ineffective, or not preferred.

Method: Data were pooled post hoc for the first 8 weeks of a phase 2b, randomized, double-blind (DB), placebo (PBO)-controlled trial (age, ≥6 to <18 y) and open-label (OL) period of a phase 3, randomized, DB, withdrawal-to-PBO trial (age, ≥6 y). These were included because ecopipam titration (3-4 weeks) and dosing (target dose, 1.8 mg/kg/day), as well as efficacy/safety measurements, were similar (there was no PBO control in phase 3 OL period). Participants who were prespecified nonresponders at Week 8 discontinued from the phase 3 OL period, preventing further analysis after this timeframe. Mean change from baseline in Yale Global Tic Severity Scale Total Tic Score (YGTSS-TTS) and adverse events (AEs) during the first 8 weeks of treatment were determined.

Results: A total of 292 ecopipam-treated participants with TS were included in the analysis. Mean (SD) age was 15.3 (7.8) y, 83.2% were aged <18 y, 70.2% were male, and baseline mean (SD) YGTSS-TTS was 34.4 (6.1). Mean (SD) change in YGTSS-TTS from baseline at Week 4 was −7.3 (7.1) and from baseline at Week 8 was −11.1 (8.0), representing a mean (SD) improvement of 21.5% (20.7) and 32.4% (22.7), respectively. A clinically meaningful improvement in tic burden (≥25% reduction in YGTSS-TTS) was seen in 35.9% (102/284) of participants at Week 4 and 69.8% (178/255) at Week 8. During the first 8 weeks of ecopipam treatment, 63.7% of the 292 participants had an AE. The most commonly reported AEs were somnolence (10.6%), headache (9.9%), fatigue (6.8%), anxiety (6.5%), tic (4.8%), and insomnia (4.5%). Two (0.7%) participants had a serious AE, and 37 (12.7%) discontinued due to an AE.

Conclusion: Clinically meaningful improvement in YGTSS-TTS was observed for a majority of participants within the first 8 weeks of starting ecopipam treatment. The safety profile during initial ecopipam treatment was similar to that of the overall trials: the most commonly reported cross-trial AEs are often observed within the first 8 weeks of exposure.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-and-effect-of-ecopipam-during-the-first-8-weeks-of-treatment-for-tourette-syndrome-a-post-hoc-analysis/