Children and adolescents with Tourette syndrome had less tic severity when treated with the investigational drug ecopipam, results from the phase IIb study showed.
Treatment with the selective dopamine-1 (D1) receptor antagonist led to a 30% drop in the study's primary endpoint, the Yale Global Tic Severity Score-Total Tic Score (), reported Atul Mahableshwarkar, MD, of Emalex Biosciences in Chicago, in a late-breaking presentation at the American Academy of Neurology 2022 annual meeting.
The difference in scores from baseline to week 12 compared with placebo was -3.44 (P=0.011) on that 50-point scale, reflecting the number, frequency, intensity, complexity, and interference of motor and phonic tics in the past week, with a standardized effect size of 0.48.
"At every time point that was measured, there was significant difference between drug and placebo," Mahableshwarkar observed.
A key secondary endpoint, the Clinical Global Impression of Tourette Syndrome Severity (), also showed a significant mean 12-week change (P=0.027).
Previous research has suggested that D1 dopamine receptors play a key role in Tourette syndrome, noted co-author Donald Gilbert, MD, of Cincinnati Children's Hospital Medical Center.
"While ecopipam is still in the testing phase, it is the first drug to target the D1 receptor instead of the D2 receptor, which is the one targeted by medications currently on the market," Gilbert said in a statement. "Our results demonstrate that ecopipam deserves more study as a viable treatment option for Tourette syndrome in young people in the future."
The study included 149 participants in its modified intent-to-treat population, 74 randomized to ecopipam 2 mg/kg/day and 75 to placebo. Study medication was titrated to the target dose over 4 weeks then maintained for an 8-week treatment period.
Mean age of participants was 12.6, and most were male. Mean baseline score on YGTSS-TTS was 34.6 in the ecopipam group, indicating moderate to severe tics.
Differences between treatment and placebo groups on the primary endpoint were significant at 12 weeks for children in both age groups: 6 to 11 years old (P=0.054) and 12 to 17 (P=0.035).
The most frequent adverse events, occurring in at least 5% of participants and more often than with placebo, were headache, insomnia, fatigue, somnolence, nasopharyngitis, anxiety, nausea, and restlessness. Overall, 3.9% of ecopipam-treated patients experienced depression, and 3.9% reported anxiety. Two participants in the ecopipam group experienced severe adverse events during the study, one with vomiting and one with COVID-19.
Ecopipam reduced Tourette syndrome tics in earlier research, including an and a of children. The FDA has granted ecopipam for the treatment of patients with Tourette syndrome.
Disclosures
This study was supported by Emalex Biosciences.
Mahableshwarkar is an employee of Emalex Biosciences.
Primary Source
American Academy of Neurology
Mahableshwarkar A, et al "Ecopipam in children and adolescents with Tourette syndrome: results from a randomized, double-blind, placebo-controlled phase 2b study" AAN annual meeting 2022.