Ecopipam Tablets to Study Tourette Syndrome in Children and Adolescents - Open Label Extension

Study Overview
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Brief Summary
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This study was an international, multicenter, open-label, long term extension study evaluating the safety of ecopipam tablets for the treatment of children and adolescent subjects with Tourette Syndrome.

Detailed Description
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This was an international, multicenter, open-label, long term extension study to evaluate the safety of ecopipam tablets for the treatment of pediatric subjects (aged ≥6 to ≤18 years at Baseline) with Tourette Syndrome. Participants who completed the Phase 2b, randomized, double-blind, efficacy and safety study (EBS-101-CL-001) without major reportable protocol deviations, and who met all the inclusion/exclusion criteria for this study were eligible to participate in this study. All participants were titrated to a target dose of 2 mg/kg/day as participants rolled over from the Phase 2b double-blind efficacy and safety study were tapered off study drug to maintain the blind from that study. Participants were to complete study visits every month for 1 year. Follow-up visits were conducted 7 and 14 days after the last dose of the study drug and a follow-up phone call was conducted 30 days after the last dose of study drug

Official Title
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A Multicenter, Open-Label, Extension Study Intended to Evaluate the Long-term Safety of Ecopipam Tablets in Children and Adolescent Subjects With Tourette's Syndrome

Conditions
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Tourette Syndrome in Children, Tourette Syndrome in Adolescence

Intervention / Treatment
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* Drug: Ecopipam


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have completed the EBS-101-CL-001 study through the Day 14 Follow Up Visit within the last 30 days (or longer with permission of the medical monitor) without a major reportable protocol deviation and must be someone the Investigator feels would benefit from continued participation. 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. Positive urine drug screen. Certain medications that would lead to drug interactions.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open Label
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ecopipam<br> | Drug: Ecopipam<br>* Ecopipam HCl 12.5-, 37.5-. 50-, 75- and 100-mg tablets; 2 mg/kg/day target dose; oral administration daily in evenings.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) and Their Relationship (Unrelated, Possibly Related, or Probably Related) | An AE was any untoward medical condition that occurs in a participant while participating in this clinical study. It can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not related to the study. An SAE was any untoward medical occurrence that at any dose met one, more of the following criteria: results in death, life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent, significant disability/incapacity, a congenital abnormality/birth defect, an important medical event. The relationship of the study drug in causing or contributing to the AE whether unrelated, possibly related, or probably related was decided by investigator medical judgment. | From start of study drug administration until 30 days after last dose (Up to Month 13) | 
| Change From Baseline in Hematology Parameters: Basophils to Leukocytes Ratio Reported in Percentage of Cells | Basophils/Leukocytes was measured in percentages (%). Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in basophils to leukocytes ratio is reported in terms of percentage of cells. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Eosinophils to Leukocytes Ratio Reported in Percentage of Cells | Eosinophils/Leukocytes was measured in percentages (%). Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in eosinophils to leukocytes ratio is reported in terms of percentage of cells. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Erythrocytes | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in hematology parameter erythrocytes was reported. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Hematocrit | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in hematology parameter hematocrit was reported. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Hemoglobin | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in hematology parameter hemoglobin was reported. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Leukocytes and Platelets | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in hematology parameters (Leukocytes and Platelets) expressed in 10^9 cells per liter were reported. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Lymphocytes to Leukocytes Ratio Reported in Percentage of Cells | Lymphocytes/leukocytes was measured in percentages (%). Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in lymphocytes to leukocytes ratio is reported in terms of percentage of cells. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Monocytes to Leukocytes Ratio Reported in Percentage of Cells | Monocytes/leukocytes was measured in percentages (%). Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in monocytes to leukocytes ratio is reported in terms of percentage of cells. | Baseline up to Month 12 | 
| Change From Baseline in Hematology Parameters: Neutrophils to Leukocytes Ratio Reported in Percentage of Cells | Neutrophils/leukocytes was measured in percentages (%). Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in neutrophils to leukocytes ratio is reported in terms of percentage of cells. | Baseline up to Month 12 | 
| Change From Baseline in Serum Chemistry Parameters: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Lactase Dehydrogenase | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in Serum chemistry parameters (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma glutamyl transferase, and lactate dehydrogenase) were reported. | Baseline up to Month 12 | 
| Change From Baseline in Serum Chemistry Parameters: Albumin, Globulin and Protein | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in Serum chemistry parameters (albumin, globulin and protein) were reported. | Baseline up to Month 12 | 
| Change From Baseline in Serum Chemistry Parameters: Bicarbonate, Calcium, Chloride, Cholesterol, Glucose, Phosphate, Potassium, Sodium, Triglyceride and Urea Nitrogen | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in Serum chemistry parameters (bicarbonate, calcium, chloride, cholesterol, glucose, phosphate, potassium, sodium, triglyceride, urea nitrogen) expressed in millimoles per liter (mmol/L) were reported. | Baseline up to Month 12 | 
| Change From Baseline in Serum Chemistry Parameters: Bilirubin, Creatinine and Direct Bilirubin | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in Serum chemistry parameters (bilirubin, creatinine and direct bilirubin) expressed in micromole per liter (mcmol/L) were reported. | Baseline up to Month 12 | 
| Change From Baseline in Hemoglobin A1c (HbA1c) | HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average blood glucose concentration over prolonged periods of time. Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in HbA1c was reported. | Baseline up to Month 12 | 
| Change From Baseline in Vital Signs Parameter: Diastolic Blood Pressure and Systolic Blood Pressure | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in vital signs parameters diastolic blood pressure and systolic blood pressure and according to the assessment position (supine and standing) expressed in millimeter(s) of mercury (mmHg) was reported. | Baseline up to Month 12 | 
| Change From Baseline in Vital Signs Parameter: Pulse Rate | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in vital sign parameter pulse rate and according to assessment position (supine and standing) was reported. | Baseline up to Month 12 | 
| Change From Baseline in Vital Signs Parameter: Body Mass Index [BMI] | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in vital signs parameter BMI was reported. | Baseline up to Month 12 | 
| Change From Baseline in Vital Signs Parameter: Height | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in vital signs height was reported. | Baseline up to Month 12 | 
| Change From Baseline in Vital Signs Parameter: Weight | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change from baseline in vital signs parameter weight was reported. | Baseline up to Month 12 | 
| Change From Baseline in Electrocardiogram (ECG) Values Parameters: Aggregate PR Interval, Aggregate QRS Duration, Aggregate QT Interval, and Aggregate QTc Interval | Baseline was defined as the last measurement taken before the first dose of open-label treatment on Day 1 of current study. Change From Baseline in ECG parameters aggregate PR interval, aggregate QRS duration, aggregate QT interval, and aggregate QTc interval expressed in millisecond (msec) was reported. | Baseline to Month 12 | 
| Number of Participants With Clinically Significant Abnormal Physical Examination Findings | Physical examination included examination of the following body areas and systems: Head, Eyes, Ears, Nose, Mouth, Throat, Neck (including Thyroid), Thorax, Abdomen, Urogenital, Extremities, Neurological, Skin and Mucosae and Others. Any clinically significant abnormalities in physical examination were judged by the investigator. Only non-zero values are reported. | Baseline up to Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Yale Global Tic Severity Scale -Total Tic Score (YGTSS-TTS) at Months 1, 3, 6, 9 and 12 | The YGTSS was a clinician-completed rating scale used to quantify overall tic severity as well as specific subdomains of tic number, frequency, intensity, complexity and interference. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a total tic score ranging from 0 to 50. Higher scores represent more severe symptoms. A negative change from baseline indicates improvement. | Baseline up to Months 1, 3, 6, 9 and 12 | 
| Change From Baseline in the Yale Global Tic Severity Scale - Impairment (YGTSS-I) at Months 1, 3, 6, 9 and 12 | The YGTSS was a clinician-completed rating scale used to quantify overall tic severity as well as specific subdomains of tic number, frequency, duration, intensity, and complexity. Each of these subdomains was scored, on 0 to 5 scale, separately for an overall impairment rating from (0 = ''none'' to 50 = ''severe''). Higher score represent more severe symptoms. A negative change from baseline indicates improvement. | Baseline up to Months 1, 3, 6, 9 and 12 | 
| Change From Baseline in the Yale Global Tic Severity Scale - Global Score (YGTSS-GS) at Months 1, 3, 6, 9 and 12 | The YGTSS was a clinician-completed rating scale used to quantify overall tic severity as well as specific subdomains of tic number, frequency, duration, intensity, and complexity. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a tic severity score ranging from 0 to 50. The YGTSS also provides for an overall impairment rating (0 = ''none'' to 50 = ''severe''). YGTSS-GS is the total of YGTSS-TTS and YGTSS-I. The maximum YGTSS Global score is 100, while the maximum motor score is 25, the maximum vocal score is 25, and the maximum impairment score is 50. Higher scores indicate more severe tics. A negative change from baseline indicates improvement. | Baseline up to Months 1, 3, 6, 9 and 12 | 
| Change From Baseline in Clinical Global Impression of Tourette Syndrome of Severity (CGI-TS-S) at Months 1, 3, 6, 9, 12 | The CGI consists of 2 reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The CGI severity scale (CGI-TS-S) ranges from 1 = not ill at all to 7 = among the most extremely ill. Higher scores represent more severe symptoms. A negative change from baseline indicates improvement. | Baseline up to Months 1, 3, 6, 9, 12 | 
| Clinical Global Impression Tourette Syndrome of Improvement (CGI-TS-I) Scores at Months 1, 3, 6, 9 and 12 | The CGI consists of 2 reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The scale ranges from 1 = very much improved to 7 = very much worse for the CGI-TS-I. Higher score represent more severe symptoms. | Months 1, 3, 6, 9 and 12 | 
| Change From Baseline in Gilles de la Tourette Syndrome-Quality of Life Scale for Children and Adolescents (C&A-GTS-QOL) Total Score at Months 1, 3, 6, 9 and 12 | The C&A-GTS-QOL was a 27-item questionnaire specific to TS patients that asks the patient to assess the extent to which their quality of life is impacted by their symptoms. The C&A-GTS-QOL consists of 6 subscales (cognitive [score range 0-32], coprophenomena [range 0-12], psychological [range 0-24], physical [range 0-12], obsessive-compulsive [range 0-16], and activities of daily living (ADL) [range 0-12] and uses a 5 point Likert scale ranging from no problem to extreme problem. Scores for six subscales were generated by summing items and, for ease of interpretation, transformation to a range of 0 to 100 (100* [(observed score-min possible score)/(max possible score-min possible score)]). Total score, resulted from sum of the subscale scores, was also normalized to a 0 to 100 range. Higher score indicated worst quality of life. A negative change from baseline indicates better quality of life. | Baseline up to Months 1, 3, 6, 9 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tourette Syndrome