Evaluation of Ecopipam Hydrochloride for Maintenance of Efficacy in Pediatric and Adolescent Patients with Tourette's Disorder: A Randomized, Double-Blind Study

The primary objective of this study is to evaluate the maintenance of **efficacy** of ecopipam tablets in children (≥ 6 and < 12 years of age) and adolescents (≥ 12 and < 18 years of age) with **Tourette’s Disorder**. This is clinically relevant as it aims to determine the long-term effectiveness of ecopipam in managing symptoms of Tourette’s Disorder in these age groups, potentially offering a sustained therapeutic option.

The secondary objectives of this study are to:

• Evaluate the safety and tolerability of ecopipam dosed at 1.8 mg/kg/day (2 mg/kg/day ecopipam HCl) in children (≥ 6 to <12 years of age), adolescents (≥ 12 and < 18 years of age), and adults (≥ 18 years of age).
• Evaluate the maintenance of efficacy of ecopipam in adults (≥ 18 years of age) with Tourette’s Disorder.
• Characterize the pharmacokinetics (PK) of ecopipam in this patient population.

These secondary objectives are crucial for understanding the broader safety profile and pharmacological behavior of ecopipam across different age groups, ensuring comprehensive data on its use in treating Tourette’s Disorder.

The clinical trial involves a total of **140 participants** diagnosed with **Tourette's Disorder**. The study population includes both male and female subjects, categorized into children aged 6 to less than 12 years and adolescents aged 12 to less than 18 years. Participants were selected based on specific inclusion criteria, including a diagnosis of Tourette's Disorder according to the DSM-5-TR criteria, and the presence of both motor and vocal tics that significantly impair normal routines. The trial population is required to have a minimum score of 20 on the YGTSS-TTS at screening and baseline visits, indicating the severity of tic symptoms. Participants must weigh at least 18 kg and, for female participants of childbearing potential, adherence to a highly effective method of contraception is mandatory during the study and for 30 days post-discontinuation of the investigational medicinal product. The study does not specify any particular lifestyle considerations such as diet or physical activity. The trial includes a vulnerable population, ensuring careful ethical considerations are in place.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the safety and maintenance of efficacy of **ecopipam hydrochloride** in children, adolescents, and adults with **Tourette's Disorder**. The trial will involve multiple study visits over an estimated duration from June 2023 to November 2024. Participants will be randomly assigned to receive either ecopipam tablets or a placebo, administered orally in tablet form. The trial will include several dosages of ecopipam, ranging from 11.2 mg to 89.6 mg, with a maximum daily dose of 200 mg and a maximum treatment period of 25 weeks.

The sequence of study visits begins with an inclusion (screening) visit, where eligibility criteria are assessed. Participants must be at least 6 years old, weigh a minimum of 18 kg, and meet the Diagnostic and Statistical Manual for Mental Disorders – 5th Edition-Text Revision (DSM-5-TR) criteria for Tourette's Disorder. They must also exhibit both motor and vocal tics that impair normal routines. Female participants of childbearing potential are required to use a highly effective method of contraception during the study and for 30 days after discontinuation of the investigational medicinal product (IMP).

Following the screening, participants will undergo a baseline visit to confirm eligibility and establish baseline measurements. The primary endpoint is the time from randomization at Week 12 to relapse in subjects aged 6 to 18 years, comparing ecopipam to placebo. Secondary endpoints include the time to relapse in all subjects, regardless of age. Follow-up visits will be conducted to monitor safety, efficacy, and any adverse events. The end-of-study visit will conclude the trial, assessing the overall outcomes and any long-term effects of the treatment.

Participant involvement is expected to last up to 25 weeks, with conditions for early termination including significant adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide valuable data on the long-term efficacy and safety of ecopipam in managing symptoms of Tourette's Disorder, contributing to the understanding and treatment of this condition.

The clinical trial involves the administration of **Ecopipam Hydrochloride** in various dosages to evaluate its efficacy and safety in treating **Tourette's Disorder**. The experimental medication is provided in tablet form and is administered orally. The trial includes several dosage strengths of Ecopipam: 11.2 mg, 22.4 mg, 33.6 mg, 44.8 mg, 67.2 mg, and 89.6 mg. Each dosage is designed to be administered daily, with the maximum daily dose varying according to the specific strength. The maximum treatment period for each dosage is 25 days. The active substance, Ecopipam Hydrochloride, is of chemical origin and is manufactured by Emalex Biosciences, Inc. The dosing schedule is structured to ensure participant compliance, with the maximum total dose amounting to 31,350 mg for the highest strength over the treatment period.

In addition to the active treatment, a placebo tablet is utilized as a comparator in this double-blind, placebo-controlled study. The placebo is designed to mimic the appearance and administration route of the active Ecopipam tablets, ensuring blinding is maintained throughout the trial. The placebo does not contain any active pharmaceutical ingredients and is used to assess the efficacy of the active treatment by comparison.

The efficacy of **ecopipam hydrochloride** in the treatment of Tourette's Disorder will be assessed in a multicenter, double-blind, placebo-controlled, randomized withdrawal study. The primary endpoint for evaluating efficacy is the time from randomization at Week 12 to relapse in subjects aged 6 to less than 18 years, comparing ecopipam to placebo during the double-blind, randomized withdrawal period. A secondary endpoint includes the time from randomization to relapse in all subjects, irrespective of age, for ecopipam compared to placebo during the same period.

Measurements will be collected at specific timepoints, with the primary assessment occurring at Week 12. The study will utilize validated scales to ensure accurate and reliable data collection. The trial is designed to evaluate the maintenance of efficacy of ecopipam tablets in children and adolescents with Tourette's Disorder, with a focus on the prevention of relapse. The study will follow a structured schedule for data collection and analysis to ensure the integrity and validity of the results.