Clinical trial NCT02102698: Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years
Official title: Ecopipam Treatment of Tourette's Syndrome in Subjects 7-17 Years
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Tourette's Syndrome
Keywords: Tourette's Syndrome
Ecopipam
D1 Receptor
Phase 2
Lead sponsor: Emalex Biosciences Inc.
Sponsor class: INDUSTRY
Collaborators: name: Psyadon Pharma
First posted: 2014-04-03
Enrollment: 40
Sex: ALL
Minimum age (years): 7
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Yale Global Tic Severity Scale
timeFrame: 30 days
Secondary outcomes:
measure: Adverse events (SAE), clinical laboratory values, regular measurement of vital signs, electrocardiograms, C-SSRS, Children's Depression Inventory and Physical Exams.
timeFrame: 30 days
measure: DuPaul ADHD rating scale-IV
timeFrame: 30 days
measure: Child Yale-Brown Obsessive Compulsive Scale
timeFrame: 30 days
measure: Children's Depression Inventory
timeFrame: 30 days
measure: Clinical Global Impression - Improvement and Severity Scales
timeFrame: 30 days
measure: Columbia-Suicide Severity Rating Scale
timeFrame: 30 days
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Saint Petersburg
country: United States
facility: University of South Florida/Rothman Center for Neuropsychiatry
state: Florida
city: Atlanta
country: United States
facility: Emory University School Of Medicine
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Medical School
state: Illinois
city: Kansas City
country: United States
facility: Children's Mercy Kansas City
state: Kansas
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Summit
country: United States
facility: Overlook Hospital
state: New Jersey
city: Manhasset
country: United States
facility: North Shore-Long Island Jewish Hosptial
state: New York
city: New York
country: United States
facility: Weill Cornell Medical School
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Donald Gilbert, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.