To determine if ecopipam increases metabolic syndrome risk and define the minimal clinically important difference (MCID) in YGTSS-TTS in children/adolescents with Tourette syndrome (TS) who completed a phase 2b randomized controlled trial (RCT) and 12-month open-label extension (OLE) study.

Dopamine-2 receptor antagonists are effective in treating TS but increase the risk of metabolic syndrome. Ecopipam, an investigational dopamine-1 receptor antagonist, significantly improved YGTSS-TTS from baseline in the RCT and OLE study (30% [Month 3] and 40% [Month 12] mean improvement, respectively).

Metabolic parameter changes during RCT and OLE were analyzed with a mixed model for repeated measures and paired t-test, respectively. ROC analysis determined the percentage improvement in YGTSS-TTS that differentiated patients with improvement on Clinical Global Impression of TS Severity (CGI-TS-S; ≥1-point decrease) or Improvement (CGI-TS-I; scores ≤3) versus no change/worsening using pooled RCT and OLE data (baseline to Week 12 of ecopipam treatment).

In RCT (n=153), there were no significant differences (ecopipam vs placebo) for mean change in weight (0.07 kg), HgA1c (−0.08%), total cholesterol (−0.07 mmol/L), triglycerides (0.02 mmol/L), or systolic/diastolic BP (1.49/1.65 mmHg; P>0.10 for all). In OLE (n=121), no significant mean change was observed for BMI Z scores (0.05), HgA1c (0.03%), total cholesterol (0.2 mmol/L), triglycerides (−0.09 mmol/L), or systolic/diastolic BP (0.26/0.91 mmHg; P>0.10 for all). ROC analysis included data from 133 patients (63.2% and 78.2% had improvement on the CGI-TS-S and CGI-TS-I, respectively). Youden’s J percentage reduction cut-offs that distinguished between improvement versus no change/worsening for YGTSS-TTS were 25.0% using CGI-TS-S as anchor and 22.9% using CGI-TS-I as anchor (AUC, 0.81 and 0.78, respectively).

Ecopipam did not adversely affect parameters associated with an increased risk of metabolic syndrome. ROC analysis suggested that ≥25% reduction in YGTSS-TTS is an appropriate minimum threshold to define clinically meaningful improvement (MCID) in this patient population.