Ecopipam Tablets to Study Tourette Syndrome in Children and Adolescents - Open Label Extension (D1AMOND)

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

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.

Study Overview

• Status: Completed
• Conditions: Tourette Syndrome in Children; Tourette Syndrome in Adolescence
• Intervention / Treatment: Drug: Ecopipam

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 124
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Ajax, Ontario, Canada, L1Z 0M1
      • The Kids Clinic Inc
    • Ottawa, Ontario, Canada, K2G 1W2
      • Center for Pediatric Excellence
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • CHU Sainte-Justine
• France
  • Poitiers, France, 86021
    • CHU Poitiers
• Germany
  • Mittweida, Germany, 09648
    • Pharmakologisches Studienzentrum Chemnitz GmbH
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Gdansk, Poland, 80-546
    • Centrum Bada Klinicznych PI-House Sp. z o.o.
  • Gdańsk, Poland, 80-542
    • Gdanskie Centrum Zdrowia Sp z o.o.
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska Synapsis
  • Krakow, Poland, 30-363
    • Centrum Medyczne Plejady
  • Krakow, Poland, 31-503
    • Wojewdzki Specjalistyczny Szpital Dziecicy im. sw. Ludwika w Krakowie
  • Poznań, Poland, 60-693
    • Med-Polonia Sp. z o. o.
• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Harmonex Neuroscience Research
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • California
    • Anaheim, California, United States, 92805
      • Advanced Research Center Inc.
    • Los Angeles, California, United States, 90095
      • UCLA
    • San Diego, California, United States, 92108
      • PCSD-Feighner Research
    • Santa Ana, California, United States, 92705
      • Syrentis Clinical Research
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale School of Medicine
  • Florida
    • Gainesville, Florida, United States, 32607
      • Sarkis Clinical Trials
    • Gulf Breeze, Florida, United States, 32561
      • Northwest Florida Clinical Research Group, LLC
    • Hialeah, Florida, United States, 33013
      • Research in Miami Inc.
    • Miami, Florida, United States, 33136
      • University of Miami
    • North Miami, Florida, United States, 33180
      • MedBio Trials
    • Orlando, Florida, United States, 32803
      • APG Research LLC
    • Saint Petersburg, Florida, United States, 33701-4825
      • University of South Florida
    • Tampa, Florida, United States, 33609-4181
      • Pediatric Epilepsy And Neurology Specialists
    • Winter Park, Florida, United States, 32789
      • Pediatric Neurology, PA
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Rare Disease Research, LLC
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60612-3841
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60637-1447
      • The University of Chicago Hospitals
    • Naperville, Illinois, United States, 60563-6510
      • AMR - Baber Research Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • Psychiatric Associates
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • Michigan Clinical Research Institute PC
    • Bloomfield Hills, Michigan, United States, 48302-1952
      • Neurobehavioral Medicine Group
    • Wyoming, Michigan, United States, 49418
      • Helen DeVos Children's Hospital / Spectrum Health Medical Group
  • Missouri
    • Saint Charles, Missouri, United States, 63304
      • St. Charles Psychiatric Associates dba Midwest Research Group
    • Saint Louis, Missouri, United States, 63110-1093
      • Movement Disorders Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • Alivation Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Center for Psychiatry and Behavioral Medicine Inc.
  • New Jersey
    • Mount Arlington, New Jersey, United States, 07856
      • The NeuroCognitive Institute
    • Voorhees, New Jersey, United States, 08043-1910
      • Clinical Research Center of NJ
  • New York
    • New York, New York, United States, 10003
      • New York Neurology Associates P.C
    • New York, New York, United States, 10019
      • Hapworth Research Inc.
    • New York, New York, United States, 10029-6504
      • Mount Sinai School of Medicine
    • New York, New York, United States, 10036
      • Mood Disorders Consulting Medicine PLLC
    • Rochester, New York, United States, 14618
      • Finger Lakes Clinical Research
  • Ohio
    • Avon Lake, Ohio, United States, 44012-1004
      • Quest Therapeutics of Avon Lake
    • Cincinnati, Ohio, United States, 45229-3026
      • Cincinnati Childrens Hospital Medical Center
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
    • Middleburg Heights, Ohio, United States, 44130
      • North Star Medical Research LLC
  • Pennsylvania
    • Media, Pennsylvania, United States, 19063
      • Suburban Research Associates
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Pediatric Research
  • Tennessee
    • Nashville, Tennessee, United States, 37203-6502
      • Access Clinical Trials, Inc.
    • Nashville, Tennessee, United States, 37232-0028
      • Vanderbilt University Medical Center
  • Texas
    • Bellaire, Texas, United States, 77401
      • Houston Clinical Trials LLC
    • Dallas, Texas, United States, 75243
      • Relaro Medical Trials
    • Fort Worth, Texas, United States, 76104
      • North Texas Clinical Trials
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78249-3539
      • Road Runner Research Ltd.
  • Utah
    • Springville, Utah, United States, 84663
      • Noetic Psychiatry
  • Virginia
    • Charlottesville, Virginia, United States, 22908-0829
      • University of Virginia
  • Washington
    • Everett, Washington, United States, 98201-4077
      • Eastside Therapeutic Resource Inc dba Core Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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: 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
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, and lactate dehydrogenase) were 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

Collaborators and Investigators

• Sponsor: Emalex Biosciences Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2019
• Primary Completion (Actual): November 11, 2022
• Study Completion (Actual): November 11, 2022

Study Registration Dates

• First Submitted: September 30, 2019
• First Submitted That Met QC Criteria: October 1, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Estimated): February 1, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Tourette Syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Disease; Genetic Diseases, Inborn; Basal Ganglia Diseases; Movement Disorders; Neurodegenerative Diseases; Heredodegenerative Disorders, Nervous System; Neurodevelopmental Disorders; Tic Disorders; Syndrome; Tourette Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Dopamine Agents; Dopamine Antagonists; Ecopipam
• Other Study ID Numbers: EBS-101-OL-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No