Tourette's Syndrome
Conditions
Keywords
Tourette's Syndrome, Ecopipam, D1 Receptor, Phase 2
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.
Interventions
DRUGEcopipam
Ecopipam is a selective antagonist of the dopamine D1 receptor family.
Sponsors
Emalex Biosciences Inc.
Psyadon Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Yale Global Tic Severity Scale - Total Tic Score | Baseline and 30 days | 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 Disorder (TD). The YGTSS is a clinician-rated, multi-dimensional instrument for assessing tic symptom severity in children and adults with TD. Both motor and vocal tics are assessed for symptom number, frequency, intensity, complexity, and interference on a 0-5 Likert scale. Scores from each dimension are totaled to reflect the severity of motor tics (range 0-25) (min of 0 to max 25), vocal tics (range 0-25) (min of 0 to max 25) and combined tics, or Total Tic Score (TTS) (range 0-50) (min of 0 to max of 50, sum of motor tics and vocal tic scores). For all scores, lower score represents better outcome. The primary outcome measure is the YGTSS-TTS (Yale Global Tic Severity Scale Total Tic Score which includes both the motor and phonic tic scores). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| YGTSS Day 16 | Baseline and Day 16 | 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 Disorder (TD). The YGTSS is a clinician-rated, multi-dimensional instrument for assessing tic symptom severity in children and adults with TD. Both motor and vocal tics are assessed for symptom number, frequency, intensity, complexity, and interference on a 0-5 Likert scale. Scores from each dimension are totaled to reflect the severity of motor tics (range 0-25) (min of 0 to max 25), vocal tics (range 0-25) (min of 0 to max 25) and combined tics, or Total Tic Score (TTS) (range 0-50) (min of 0 to max of 50, sum of motor tics and vocal tic scores). For all scores, lower score represents better outcome. The outcome measure described is the YGTSS-TTS (Yale Global Tic Severity Scale Total Tic Score which includes both the motor and phonic tic scores) at Day 16 vs baseline. |
| DuPaul ADHD (Attention Deficit Hyperactivity Disorder) Rating Scale-IV | Baseline and 30 days | This is a validated rating scale for the symptoms of attention deficit disorder. Scale includes 18 core items, with higher score indicating greater severity of ADHD (Total score 0-54). These scores are compared from baseline and 30 days below; There are also subscales but not individually shown. The subscales include 9 items measured for Inattention; 9 for Hyperactivity/Impulsivity. A score of 2 or 3 on any item is considered clinically significant. Measure on 4-point Likert scale and also include optional performance items. Raw scores are summed for each subscale. Scores are compared to norm-referenced percentiles based on age and gender. Higher scores may indicate ADHD. |
| Child Yale-Brown Obsessive Compulsive Scale | Baseline and 30 days | The CY-BOCS is a clinician-rated, 10-item scale to both determine severity of OCD and to monitor improvement during treatment, with a higher score indicating greater severity. The scale is a clinician-rated, 10-item scale (5 items regarding severity and 5 items regarding obsessions) that includes questions about the amount of time spent on obsessions/compulsions, level of impairment or distress, and how much resistance and control subjects have over these thoughts. The 10 items are assessed on a 6-point scale with an overall score. Total score from 0 to 40 with higher score indicating greater severity. Total score change shown below. |
| Clinical Global Impression Scale - Severity | Baseline and 30 days | 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). The CGI consists of two reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The severity scale (CGI-S) ranges from 1 (Normal, not ill) to 7 (extremely ill). The improvement scale (CGI-I) ranges from 1 (very much improved) to 7 (very much worse) with a score of 1 or 2 defining positive response. The improvement rating compares the subject's overall clinical condition to the Baseline visit and the rater should consider the following question: "Compared to tic severity at baseline, how much has the subject changed?" Data shows how much improvement at Day 30 with Ecopipam vs Placebo. |
Countries
United States
Contacts
STUDY_CHAIRDonald Gilbert, MD
Children's Hospital Medical Center, Cincinnati
Participant flow
Recruitment details
First subject enrolled 19Jun2014 and last subject enrolled 17Nov2016
Pre-assignment details
19 in Ecopipam/Placebo arm and 21 in Placebo/Ecopipam arm
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 40 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 19 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 40 |
| other Total, other adverse events | 32 / 40 | 26 / 40 |
| serious Total, serious adverse events | 0 / 40 | 1 / 40 |
Outcome results
None listed