Ecopipam demonstrated clinically meaningful reduction of tics by 30% in children and adolescents with Tourette syndrome without causing adverse events commonly seen in other treatments, according study findings published in journal Pediatrics.
Previous clinical trials have shown that ecopipam, a selective, dopamine-1 receptor (D1r) antagonist, demonstrated effectiveness in reducing tics in both children and adults with Tourette syndrome without prior evidence to this effect.
Researchers across the United States, Canada, Germany, France, and Poland conducted a phase 2b, multicenter, double-blind, randomized, placebo-controlled trial between May 2019 and September 2021 to evaluate the efficacy and safety of ecopipam in the treatment of children and adolescents aged between 6-18 years with Tourette syndrome. They were particularly interested in learning whether ecopipam could achieve a clinically meaningful reduction in tics while demonstrating less side effects as seen in currently approved D2-like receptor (D2r) antagonist treatments.
The researchers randomly allocated 153 children and adolescents with Tourette syndrome into 2 groups: the treatment group (n=76) who received 2 mg/kg/day of ecopipam and the control group (n=77) who received a matching placebo. Both groups underwent a 4-week titration followed by an 8-week treatment period. Approximately 10.5% of study participants discontinued the trial prematurely due to adverse events and withdrawal by a parent or caregiver.
Tic severity was measured at baseline and again at weeks 4, 6, 8, and 12, using the Yale Global Tic Severity Score, Total Tic Score (YGTSS-TTS). Secondary outcome measures included changes in the:
- Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S),
- Clinical Global Impression of Tourette Syndrome Improvement (CGI-TS-I),
- Caregiver Global Impression of Change (CaGI-C),
- Gilles de la Tourette Syndrome Quality of Life Scale for Children and Adolescents (C&A-GTS-QoL), and
- the proportion of patients who achieved 25% or greater improvement on the YGTSS-TTS, indicating a clinically meaningful change.
Adverse drug-related side effects were assessed at 7, 14, and 30 days following the last administration of ecopipam.
After 12 weeks, children and adolescents treated with ecopipam demonstrated clinically significant improvement as shown by a 30% reduction of tics based on YGTSS-TTS score changes (mean difference from baseline: -3.44; 95% CI, -6.09 to -0.79; P =.01). Significant benefits were observed by week 4 and continued throughout the course of treatment in the ecopipam group.
Compared with the placebo group, the ecopipam group demonstrated clinically meaningful improvements of 25% or more on the YGTSS-TTS (73.6% vs 43.2%; odds ratio [OR], 3.7; 95% CI, 1.8-7.4; P <.001).
Scores on the CGI-TS-S improved significantly in the treatment group compared with baseline measurements (mean difference: -0.37; 95% CI, -0.70 to -0.04; P =.03). The researchers observed nominally significant improvement on the CaGI-C scores (P <.01); however, the changes in the CGI-TS-I and C&A-GTS-QoL scores after 12 weeks did not differ significantly between the treatment and placebo groups.
The most frequently reported adverse events included headaches (15.8%), insomnia (14.5%), fatigue (7.9%), and somnolence (7.9%). Most adverse events were mild to moderate in nature. In the treatment group, the most serious adverse events included COVID-19 infection (n=1) and vomiting due to inflammatory bowel syndrome, both of which were deemed unrelated to treatment.
Suicidal ideation occurred more frequently in the placebo group (10.4%). In contrast, no patients in the treatment group experienced suicidal ideations while receiving treatment.
Additionally, children and adolescents with Tourette syndrome in the placebo group demonstrated increased weight gain compared with the treatment group. Metabolic or electrocardiogram changes did not occur while taking ecopipam, whereas treatment of Tourette syndrome with approved D2r antagonists increases risk for weight gain, diabetes, dyslipidemia, and elevated prolactin levels.
“In summary, ecopipam revealed significant and clinically meaningful improvement in TS [Tourette syndrome] on the basis of clinician ratings of tics and overall symptom severity,” the researchers noted. “Ecopipam may be a safe and effective treatment of TS with advantages over other currently approved therapeutic agents,” they added.
Study limitations included lack of racial and ethnic diversity, lack of assessment of efficacy and safety of ecopipam beyond 12 weeks, and lack of generalizability to adults given this trial including only children and adolescents.
Disclosures: Several study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see original source for full list of disclosures.
Gilbert DL, Dubow JS, Cunniff TM, Wanaski SP, Atkinson SD, Mahableshwarkar AR. Ecopipam for Tourette syndrome: a randomized trial. Pediatrics. Published online January 11, 2023. doi:10.1542/peds.2022-059574