Tourette Syndrome
Conditions
Brief summary
This study evaluates the effect of ecopipam tablets in children and adolescents in the treatment of Tourette's Syndrome (TS). Half of the participants will receive ecopipam tablets, while the other half will receive matching placebo tablets
Detailed description
Multicenter, placebo-controlled, double-blind, randomized, parallel-group, Phase 2b study in pediatric subjects (aged greater than equal to 6 to less than 18 years of age) with TS. Following a 28-day Screening period and Baseline visit, eligible subjects will be randomized 1:1 to receive either ecopipam hydrochloride (HCl) or matching placebo for a 12 week treatment period. Doses will be titrated up and down from target dose of 2 mg/kg/day. Follow Up visit will be conducted after the last dose of study medication.
Interventions
DRUGEcopipam
Ecopipam HCI tablets administered PO to establish 2 mg/kg/day
DRUGPlacebo
Matching Placebo
Sponsors
Emalex Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 6 and \< 18 years of age * ≥ 18 kg (\ 40 lbs.) * TS diagnosis and both motor and vocal tics that cause impairment with normal routines * Minimum score of 20 on the YGTSS-Total Tic Score * May not be taking any medications used to treat motor or vocal tics for at least 14 days prior to Baseline. * Effective contraception during the study and 30 days after last study dose for sexually active subjects
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 * Hepatic insufficiency * Positive urine drug screen * Unstable doses for drugs to treat anxiety, depression, Attention Deficit Hyperactivity Disorder * Certain medications that would lead to drug interactions * Recent behavioral therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12 | Baseline, Week 12 | The YGTSS was a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0=none to 5=severe for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms. A negative change from baseline indicates improvement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12 | Baseline, Week 12 | Clinical Global Impression (CGI) scale was used to assess overall severity on a 7-point Likert scale consisted of 2 reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The CGI severity scale ranges from 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill subject. 1 = normal, not ill at all to 7 = extremely ill. A negative change indicates improvement in the condition. |
Countries
Canada, France, Germany, Poland, United States
Participant flow
Recruitment details
The study was conducted at 45 sites in 5 countries (United States, Canada, Germany, France, and Poland) from 28 June 2019 (first participant first visit) and 23 September 2021 (last participant last visit).
Pre-assignment details
A total of 215 participants were screened, of which 61 participants were screen failures and 153 participants were randomized in 1:1 ratio to receive ecopipam HCl and placebo.
Participants by arm
| Arm | Count |
|---|---|
| Ecopipam HCI 2 mg/kg/Day Participants received a targeted steady-state dose of 2 milligram per kilogram per day (mg/kg/day) of ecopipam HCl tablets orally, once daily during a titration and treatment period for a total of 12 weeks. | 76 |
| Placebo Participants received matching placebo tablets orally, once daily during a titration and treatment period for a total of 12 weeks. | 77 |
| Total | 153 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse event, non-fatal | 5 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Non-compliance with Study Drug | 0 | 1 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Parent/Caregiver | 1 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Ecopipam HCI 2 mg/kg/Day | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 12.6 years STANDARD_DEVIATION 2.78 | 12.6 years STANDARD_DEVIATION 2.63 | 12.6 years STANDARD_DEVIATION 2.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 11 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 63 Participants | 66 Participants | 129 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 6 Participants | 3 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 66 Participants | 72 Participants | 138 Participants |
| Sex: Female, Male Female | 17 Participants | 24 Participants | 41 Participants |
| Sex: Female, Male Male | 59 Participants | 53 Participants | 112 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 77 |
| other Total, other adverse events | 47 / 76 | 38 / 77 |
| serious Total, serious adverse events | 2 / 76 | 1 / 77 |
Outcome results
Primary
Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12
The YGTSS was a semi-structured clinical interview designed to measure the tic severity. This scale consisted of a tic inventory, with 5 separate rating scales to rate the severity of symptoms, and an impairment ranking. Ratings were made along 5 different dimensions on a scale of 0=none to 5=severe for motor and vocal tics, each including number, frequency, intensity, complexity, and interference. The YGTSS TTS was the summation of the severity scores of motor and vocal tics. The total tic score (TTS) ranged from 0 (none) to 50 (severe) with higher score represent more severe symptoms. A negative change from baseline indicates improvement.
Time frame: Baseline, Week 12
Population: The mITT set included all randomized participants who received at least 1 dose of study drug and had at least 1 post-baseline scoring of the YGTSS.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ecopipam HCI 2 mg/kg/Day | Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12 | -9.87 score on a scale | Standard Error 1.062 |
| Placebo | Change From Baseline in the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) at Week 12 | -6.42 score on a scale | Standard Error 1.006 |
p-value: =0.01195% CI: [-6.09, -0.79]ANCOVA
Secondary
Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12
Clinical Global Impression (CGI) scale was used to assess overall severity on a 7-point Likert scale consisted of 2 reliable and valid 7-item Likert scales used to assess severity and change in clinical symptoms. The CGI severity scale ranges from 1 = Normal, not at all ill; 2 = Borderline ill; 3 = Mildly ill; 4 = Moderately ill; 5 = Markedly ill; 6 = Severely ill; 7 = Among the most extremely ill subject. 1 = normal, not ill at all to 7 = extremely ill. A negative change indicates improvement in the condition.
Time frame: Baseline, Week 12
Population: The mITT set included all randomized subjects who received at least 1 dose of study drug and had at least 1 post-baseline scoring of the YGTSS. Here, Overall Number of Participants Analyzed signifies participants who were evaluable for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Ecopipam HCI 2 mg/kg/Day | Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12 | -0.91 score on a scale | Standard Error 0.141 |
| Placebo | Change From Baseline in Clinical Global Impression of Tourette Syndrome Severity (CGI-TS-S) at Week 12 | -0.53 score on a scale | Standard Error 0.13 |