Objective: Determine if ecopipam is associated with the emergence of clinical features suggestive of metabolic syndrome in pediatric subjects with Tourette Syndrome (TS)

Background: Dopamine-2 (D2) receptor antagonists are effective in treating moderate to severe TS. However, this class of drugs increases the risk of metabolic syndrome: weight gain, hypertension, hyperglycemia, and dyslipidemia. Ecopipam is a selective Dopamine-1 (D1) receptor antagonist under investigation for TS. In a Phase IIb, randomized, placebo controlled study, ecopipam significantly (p=0.01) improved tics, rated with the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS). Subjects completing the Phase 2b study could enter a 12-month Open-Label Extension (OLE) study to inform longer term safety and activity. In the OLE study, YGTSS-TTS scores significantly improved from baseline at all timepoints (p<0.0001). Headache (9.2%), fatigue (6.6%), somnolence (6.6%), insomnia (5.3%), and restlessness (5.3%) were the most common treatment-related adverse reactions.

Method: A total of 153 subjects aged 6 to 18 (mean 12.8) years entered Phase 2b and 121 subjects entered the OLE. We assessed changes in weight, systolic and diastolic blood pressure (BPs, BPd), HgbA1c, total cholesterol, triglycerides, and z-scores for body mass index (BMI) derived from age and gender matched CDC data. A mixed model for repeated measures was used to assess changes in the P2b study. A paired t-test was used to assess changes in the OLE study.

Results: In the P2b 12-week study we found no significant difference (ecopipam – placebo) in mean change for: weight, 0.07 kg, p=0.97; BPs, 1.49 mmHg, p=0.39; BPd, 1.65 mmHg, p=0.28; HgbA1c -0.08 %, p= 0.11; total cholesterol, -0.07 SI units, p= 0.38; triglycerides, 0.02 SI units, p=0.86. During the 12-month OLE study, there were no significant changes in BPs, 0.26 mmHg, p=0.85; BPd, 0.91 mmHg, p=0.44; HgbA1c, 0.03 %, p=0.60; total cholesterol, 0.20 SI units, p= 0.14; BMI z-scores, 0.05, p=0.35.

Conclusion: In both the 12-week P2b study and the 12-month OLE study, ecopipam, a selective D1 receptor antagonist, significantly improved the YGTSS-TTS without adversely affecting weight, BMI, HgbA1c, lipids, or BP. There is no evidence that ecopipam increases the risk of metabolic syndrome.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ecopipam-does-not-adversely-affect-metabolic-parameters-in-pediatric-subjects-with-tourette-syndrome-results-from-a-phase-2b-with-12-month-open-label-extension-study/