Ecopipam Tablets to Study Tourette's Syndrome in Children and Adolescents

Multicenter, placebo-controlled, double-blind, randomized, parallel-group, Phase 2b study in pediatric subjects (aged greater than equal to 6 to less than 18 years of age) with TS. Following a 28-day Screening period and Baseline visit, eligible subjects will be randomized 1:1 to receive either ecopipam hydrochloride (HCl) or matching placebo for a 12 week treatment period. Doses will be titrated up and down from target dose of 2 mg/kg/day. Follow Up visit will be conducted after the last dose of study medication.

• Ecopipam (Drug): Ecopipam HCI tablets administered PO to establish 2 mg/kg/day
• Placebo (Drug): Matching Placebo

Primary outcomes

• Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12 [Baseline, Week 12]: The YGTSS was a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0=none to 5=severe for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms. A negative change from baseline indicates improvement.

Secondary outcomes

• Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12 [Baseline, Week 12]: Clinical Global Impression (CGI) scale was used to assess overall severity on a 7-point Likert scale consisted of 2 reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The CGI severity scale ranges from 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill subject. 1 = "normal, not ill at all" to 7 = "extremely ill." A negative change indicates improvement in the condition.

Sex: All, ages: 6 Years to 17 Years

Inclusion Criteria:

* ≥ 6 and < 18 years of age
* ≥ 18 kg (\~ 40 lbs.)
* TS diagnosis and both motor and vocal tics that cause impairment with normal routines
* Minimum score of 20 on the YGTSS-Total Tic Score
* May not be taking any medications used to treat motor or vocal tics for at least 14 days prior to Baseline.
* Effective contraception during the study and 30 days after last study dose for sexually active subjects

Exclusion Criteria:

* Certain mood or psychiatric disorders (i.e., dementia, bipolar disorder, schizophrenia, major depressive disorder)
* Unstable medical illness or clinically significant lab abnormalities
* Risk of suicide
* Pregnant or lactating women
* Moderate to severe renal insufficiency
* Hepatic insufficiency
* Positive urine drug screen
* Unstable doses for drugs to treat anxiety, depression, Attention Deficit Hyperactivity Disorder
* Certain medications that would lead to drug interactions
* Recent behavioral therapy

Participant flow

Outcome results

• Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12 (Primary), Least squares mean, score on a scale: Ecopipam HCI 2 mg/kg/Day -9.87 +/- 1.062; Placebo -6.42 +/- 1.006 (p =0.011)
• Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12 (Secondary), Least squares mean, score on a scale: Ecopipam HCI 2 mg/kg/Day -0.91 +/- 0.141; Placebo -0.53 +/- 0.130

Adverse events

Time frame: Screening up to 30 days after the last dose ( up to Week 16)

Serious adverse events by term

Other adverse events by term

• Study Protocol (PDF, 2020-04-13)
• Statistical Analysis Plan (PDF, 2021-09-23)