Clinical trial NCT01244633: Ecopipam Treatment of Tourette Syndrome
Official title: Ecopipam Treatment of Tourette Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tourette's Syndrome
Keywords: Tourette's
Ecopipam
Dopamine receptors
Efficacy
Safety
Adults
Lead sponsor: Psyadon Pharma
Sponsor class: INDUSTRY
First posted: 2010-11-19
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Tourette's Syndrome is a neurological disease characterized by verbal and motor tics. The currently available drug treatments are considered to be inadequate. This clinical trial is designed to test if ecopipam is effective for the treatment of Tourette's Syndrome in adults.

Detailed description: Tourette's Syndrome is a neurological disease characterized by verbal and motor tics. Although its causes are unknown, many researchers believe that changes in brain chemicals (called neurotransmitters) are critically involved. One of these neurotransmitters is called dopamine, and it exerts its actions through its receptors (called D1-type or D2-type). It has been suggested that the symptoms of Tourette's Syndrome are due to an overactivity at the D1-type receptor. Ecopipam is a selective antagonist of the D1-type receptors. The present clinical trial is designed to test if ecopipam is able to relieve the symptoms of the disease in adults patients with Tourette's Syndrome. Eligible patients will be treated for eight weeks.

Eligibility criteria: Inclusion Criteria:

* Subjects must have TS (Tourette's Syndrome) based on the clinician-administered DCI (Diagnostic Confidence Index) for TS.
* Subjects must exhibit both motor and vocal tics.
* Subjects must have exhibited tics for \>5 years.
* Subjects must have a minimum score of 20 at both Screening and Baseline (just prior to the first treatment) on the YGTSS (Yale Global Tic Severity Score).
* Subjects must be age ≥ 18 years.
* Women must be postmenopausal (\> 12 months without menses) or surgically sterile (i.e., by hysterectomy and/or bilateral oophorectomy) or 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. Women of childbearing potential must 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 must execute a written informed consent.

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 (score of ≥ 2 on Item 3 for the Hamilton Depression Rating Scale \[HAM-D\])
* Subjects with a first-degree relative with a major depressive episode that resulted in any psychiatric hospitalization, attempted or completed suicide
* Subjects with a history of seizures.
* Subjects with a myocardial infarction within 6 months.
* Women of childbearing potential 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, naltrexone, methylphenidate, or psychostimulants), unfavorable interactions with ecopipam (ie, dopamine agonists \[including bupropion\]), 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 Statistical Manual IV Text Revision (DSM-IV-TR) 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 or depot neuroleptics within 3 months
  * fluoxetine within 6 weeks
  * other psychotropics with possible effects on TS symptoms (ie, lithium, or naltrexone) within 2 weeks prior to Screening.
  * oral neuroleptics within 2 weeks
  * selective serotonin reuptake inhibitors unless the dosage has been stable for a minimum of 4 weeks prior to study start

Primary outcomes:
measure: Yale Global Tic Severity Score
timeFrame: 8 weeks
Secondary outcomes:
measure: Adult Attention Deficit/Hyperactivity Disorder (ADHD) Self-report Symptom Checklist (ASRS)
timeFrame: Every 7 days
measure: Hamilton Depression Scale
timeFrame: Every 7 days
measure: Premonitory Urge for Tics Scale (PUTS-1)
timeFrame: Every 7 days
measure: Clinician Global Impression - Improvement and Severity Scales (CGI)
timeFrame: End of trial
measure: Safety Assessments
timeFrame: Every 7 days
measure: Columbia Scale for Suicide Risk
timeFrame: Every 7 days
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University
state: Maryland
city: Summit
country: United States
facility: Atlantic Neuroscience Institute Overlook Hospital
state: New Jersey
city: Manhasset
country: United States
facility: North Shore Hospital
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Donald Gilbert, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chipkin RE, Iorio LC, Coffin VL, McQuade RD, Berger JG, Barnett A. Pharmacological profile of SCH39166: a dopamine D1 selective benzonaphthazepine with potential antipsychotic activity. J Pharmacol Exp Ther. 1988 Dec;247(3):1093-102.