Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years

Tourette's Syndrome is a neurological disease characterized by motor and vocal tics. It has been hypothesized that abnormal interactions of dopamine with its receptors may cause the tics. The purpose of this study is to test the hypothesis that a drug (ecopipam) that selectively blocks dopamine D1/D5 receptors can reduce the frequency and severity of the tics.

Study Overview

• Status: Completed
• Conditions: Tourette's Syndrome
• Intervention / Treatment: Drug: Ecopipam

Detailed Description

This is a double blind, randomized, placebo-controlled crossover study to determine whether ecopipam can reduce the symptoms of Tourette's in children age 7-17 years.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • UCLA
  • Florida
    • Saint Petersburg, Florida, United States, 33701
      • University of South Florida/Rothman Center for Neuropsychiatry
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University School Of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical School
  • Kansas
    • Kansas City, Kansas, United States, 64108
      • Children's Mercy Kansas City
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Summit, New Jersey, United States, 07902
      • Overlook Hospital
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore-Long Island Jewish Hosptial
    • New York, New York, United States, 10065
      • Weill Cornell Medical School
  • Ohio
    • Cincinnati, Ohio, United States, 45228
      • Cincinnati Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:• Subjects must have Tourette's Syndrome (TS) based on the clinician-administered Diagnostic Confidence Index (DCI) for TS.

• Subjects must exhibit both motor and vocal tics.
• Subjects must have a minimum score of 20 at both Screening and Baseline (just prior to the first treatment) on the Yale Global Tic Severity Scale.
• Subjects must be age (≥ 7 to < 18 years of age)
• Subjects must weigh ≥ 20 kg (45 lbs)
• Adolescent females of childbearing potential who are sexually active must be using effective contraception (i.e., oral contraceptives, intrauterine device, double barrier method of condom and spermicide) and agree to continue use of contraception for the duration of their participation in the study. They must also agree to use contraception for 30 days after their last dose of study drug.
• Sexually active male subjects must use a barrier method of contraception during the study and agree to continue the use of male contraception for at least 30 days after the last dose of study drug.
• Subject's parent or legal guardian must execute a written informed consent.
• Subject must execute a written informed assent.

Exclusion Criteria:

• Subjects who have unstable medical illness or clinically significant abnormalities on laboratory tests, or ECG at Screening.
• Subjects with a major depressive episode in the past 2 years
• Subjects with a history of attempted suicide
• Subjects with clinically significant suicidality (based on the Columbia Suicide Rating Scale (C-SSRS)
• Subjects with a first-degree relative with a major depressive episode that resulted in any psychiatric hospitalization, or attempted/ completed suicide with the exception of a hospitalization for post-partum depression.
• Subjects with a history of seizures (excluding febrile seizures that occurred >2 years in the past)
• Subjects with a myocardial infarction within 6 months.
• Girls who are currently pregnant or lactating.
• Subjects who have a need for medication (other than ecopipam) with possible effects on TS symptoms (i.e., lithium, psychostimulants)
• Subjects who have a need for medications which would have unfavorable interactions with ecopipam, e.g., dopamine antagonists or agonists [including bupropion], tetrabenazine, or monoamine oxidase inhibitors.
• Subjects with a lifetime history of bipolar disorder type I or II, dementia, schizophrenia, or any psychotic disorder determined by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders - 4th Edition (DSM-IV) Axis-I Disorders (SCID).
• Subjects with current or recent (past 3 months) DSM-IV substance abuse or dependence (with the exception of nicotine).
• Subjects with positive urine drug screen (cocaine, amphetamine, methamphetamine, tetrahydrocannabinol (THC), benzodiazepines, barbiturates, phencyclidine (PCP), opiates) at Screening. Subjects with urine positive only for benzodiazepines and/or marijuana (i.e., a user but not an abuser as based on DSM-IV criteria) may be eligible.
• Subjects who have had previous treatment with ecopipam.

• Subjects who have had treatment with:

  • investigational medication within 3 months of starting study
  • depot neuroleptics within 3 months of starting study
  • other psychotropics with possible effects on TS symptoms (i.e., lithium, tetrabenazine) within 2 weeks prior to Screening.
  • oral neuroleptics within 4 weeks
  • selective serotonin reuptake inhibitors unless the dosage has been stable for a minimum of 4 weeks prior to study start and not prescribed to relieve the neurological signs of TS

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ecopipam; Ecopipam is a selective antagonist of the dopamine D1/D5 receptor family that is being studied as a treatment for Tourette's Syndrome	Drug: Ecopipam; Ecopipam is a selective antagonist of the dopamine D1 receptor family.; Other Names: SCH 39166; PSYRX101
Placebo Comparator: Placebo; Placebo is the inactive comparator	Drug: Ecopipam; Ecopipam is a selective antagonist of the dopamine D1 receptor family.; Other Names: SCH 39166; PSYRX101

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Yale Global Tic Severity Scale	The Yale Global Tic Severity Scale (YGTSS) is the standard rating scale used to assess the effects of a new treatment on the symptoms of Tourette's Syndrome.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DuPaul ADHD rating scale-IV	This is a validated rating scale for the symptoms of attention deficit disorder. This is included because people with Tourette's often have attention deficit hyperactivity disorder (ADHD) as well.	30 days
Child Yale-Brown Obsessive Compulsive Scale	This is validated rating scale which measures symptoms of obsessive-compulsive behaviors. People with Tourette's often also show symptoms of obsessive-compulsive behaviors.	30 days
Children's Depression Inventory	The Children's Depression Inventory is a validate rating scale which measures signs of depression of in children. People with Tourette's often report feelings of depression. In addition, treatment with ecopipam has been reported to increase signs of depression in some patients.	30 days
Clinical Global Impression - Improvement and Severity Scales	Clinical Global Impression Scales (improvement and severity) are validated rating scales that measure whether the treatment improves the symptoms of the disease (CGI-I) and whether the treatment reduces the severity of the disease (CGI-S)	30 days
Columbia-Suicide Severity Rating Scale	The Columbia Suicide Severity Rating Scale is a validated rating scale which measures feelings of suicide.	30 days
Adverse events (SAE), clinical laboratory values, regular measurement of vital signs, electrocardiograms, C-SSRS, Children's Depression Inventory and Physical Exams.	Safety evaluations are included.	30 days

Collaborators and Investigators

• Sponsor: Emalex Biosciences Inc.
• Collaborators: Psyadon Pharma
• Investigators: Study Chair: Donald Gilbert, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

General Publications

• Gilbert DL, Budman CL, Singer HS, Kurlan R, Chipkin RE. A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome. Clin Neuropharmacol. 2014 Jan-Feb;37(1):26-30. doi: 10.1097/WNF.0000000000000017.
• Gilbert DL, Murphy TK, Jankovic J, Budman CL, Black KJ, Kurlan RM, Coffman KA, McCracken JT, Juncos J, Grant JE, Chipkin RE. Ecopipam, a D1 receptor antagonist, for treatment of tourette syndrome in children: A randomized, placebo-controlled crossover study. Mov Disord. 2018 Aug;33(8):1272-1280. doi: 10.1002/mds.27457. Epub 2018 Sep 7.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: March 31, 2014
• First Submitted That Met QC Criteria: March 31, 2014
• First Posted (Estimated): April 3, 2014

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Tourette's Syndrome; Phase 2; Ecopipam; D1 Receptor
• 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: PSY302