Tourette Disorder
Conditions
Brief summary
This Phase 3 multicenter study evaluates the maintenance of efficacy, safety and tolerability of ecopipam tablets in children, adolescents and adults in the treatment of Tourette's Disorder (TD). The study includes an open-label period followed by a double-blind, placebo-controlled, randomized withdrawal period.
Detailed description
Following a 28-day Screening period and Baseline visit, eligible subjects will be enrolled into the open-label Stabilization period comprised of a 4-week Titration phase to achieve a target steady-state dose of 1.8 mg/kg/day ecopipam (2 mg/kg/day ecopipam HCl) followed by an 8-week open-label Maintenance phase. Responders to ecopipam will be randomized to ecopipam 1.8 mg/kg/day (2 mg/kg/day ecopipam HCl) or placebo in a 1:1 fashion and enter the double-blind Randomized-Withdrawal (R/WD) period at Week 12. During the 12-week R/WD period, any subject meeting Relapse criteria will be withdrawn from blinded study medication and complete end of study assessments including safety follow up visits.
Interventions
Selective dopamine D1 and D5 receptor antagonist
Sponsors
Emalex Biosciences Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This includes an open-label period followed by a double-blind, placebo-controlled, randomized withdrawal period.
Intervention model description
Sequential Assignment This is a multicenter study which includes an open-label period followed by double-blind, placebo-controlled, randomized withdrawal period.
Eligibility
Sex/Gender
ALL
Age
6 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 6 years of age * ≥ 18 kg (\~ 40 lbs.) * TD diagnosis and both motor and vocal tics that cause impairment with normal routines * Minimum score of 20 on the YGTSS-R 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
* Previous exposure to ecopipam * 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 |
|---|---|---|
| Time From Randomization to Relapse in Participants Greater Than and Equal to (>=) 6 and Less Than (<) 18 Years During the Double-Blind R/WD | From randomization at Week 12 through the end of the double-blind R/WD period (up to Week 24) | Time to relapse defined as a loss of \>=50 percent (%) of the improvement experienced on the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) from Baseline to the last visit in the Open-Label Stabilization Period (Week 12), or initiation of additional medications to treat symptoms of Tourette's Disorder (TD), or requirement of hospitalization for worsening symptoms of TD in participants between the ages of \>= 6 and \<18 years for ecopipam compared to those receiving placebo during the double-blind, R/WD period. The YGTSS was a clinician-completed rating scale used to quantify overall tic severity in participants with TD as well as specific subdomains of tic number, frequency, intensity, complexity and interference. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a total tic score ranging from 0 to 50. Higher scores represented more severe symptoms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to Relapse in All Participants During the Double-Blind R/WD Period | From randomization at Week 12 through the end of the double-blind R/WD period (up to Week 24) | Time From Randomization (Week 12) to relapse defined as a loss of \>= 50% of the improvement experienced on the YGTSS-TTS from Baseline to the last visit in the Open-Label Stabilization Period (Week 12), or initiation of additional medications to treat symptoms of TD, or requirement of hospitalization for worsening symptoms of TD in all participants during the Double-Blind R/WD period for ecopipam compared to placebo. The YGTSS was a clinician-completed rating scale used to quantify overall tic severity in children and adults with TD as well as specific subdomains of tic number, frequency, intensity, complexity and interference. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a total tic score ranging from 0 to 50. Higher scores represented more severe symptoms. |
Countries
Bulgaria, Canada, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Serbia, Spain, United States
Participant flow
Recruitment details
The multicenter study was conducted globally in the United States, Bulgaria, Canada, Denmark, France, Germany, Hungary, Italy, Poland, Romania, Serbia, and Spain from 31 January 2023 to 04-February 2025.
Pre-assignment details
Participants with a diagnosis of Tourette's Disorder were enrolled in this study to receive oral ecopipam in an Open-label Stabilization Period and a Double-blind Randomized Withdrawal (R/WD) Period and then followed for safety up to 30 days post-last dose.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Stabilization Period: Ecopipam 1.8 mg/kg/Day All participants in the open-label stabilization period who received a target steady-state dose of 1.8 mg/kg/day ecopipam (2 mg/kg/day ecopipam hydrochloride \[HCl\]) tablets based on body weight, administered orally, once daily in the evening during a 4-week titration phase and further followed by an 8-week maintenance phase. | 216 |
| Total | 216 |
Baseline characteristics
| Characteristic | Open-label Stabilization Period: Ecopipam 1.8 mg/kg/Day |
|---|---|
| Age, Continuous | 16.3 years STANDARD_DEVIATION 8.76 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 29 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 186 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 7 Participants |
| Race (NIH/OMB) More than one race | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 196 Participants |
| Sex: Female, Male Female | 70 Participants |
| Sex: Female, Male Male | 146 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 216 | 0 / 51 | 0 / 53 |
| other Total, other adverse events | 140 / 216 | 20 / 51 | 22 / 53 |
| serious Total, serious adverse events | 1 / 216 | 1 / 51 | 2 / 53 |
Outcome results
Primary
Time From Randomization to Relapse in Participants Greater Than and Equal to (>=) 6 and Less Than (<) 18 Years During the Double-Blind R/WD
Time to relapse defined as a loss of \>=50 percent (%) of the improvement experienced on the Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) from Baseline to the last visit in the Open-Label Stabilization Period (Week 12), or initiation of additional medications to treat symptoms of Tourette's Disorder (TD), or requirement of hospitalization for worsening symptoms of TD in participants between the ages of \>= 6 and \<18 years for ecopipam compared to those receiving placebo during the double-blind, R/WD period. The YGTSS was a clinician-completed rating scale used to quantify overall tic severity in participants with TD as well as specific subdomains of tic number, frequency, intensity, complexity and interference. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a total tic score ranging from 0 to 50. Higher scores represented more severe symptoms.
Time frame: From randomization at Week 12 through the end of the double-blind R/WD period (up to Week 24)
Population: The modified intention-to-treat (mITT) set included all randomized participants who received at least 1 dose of study drug post-randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double- Blind R/WD Period: Ecopipam 1.8 mg/kg/Day | Time From Randomization to Relapse in Participants Greater Than and Equal to (>=) 6 and Less Than (<) 18 Years During the Double-Blind R/WD | NA weeks |
| Double- Blind R/WD Period: Placebo | Time From Randomization to Relapse in Participants Greater Than and Equal to (>=) 6 and Less Than (<) 18 Years During the Double-Blind R/WD | 4.0 weeks |
Secondary
Time From Randomization to Relapse in All Participants During the Double-Blind R/WD Period
Time From Randomization (Week 12) to relapse defined as a loss of \>= 50% of the improvement experienced on the YGTSS-TTS from Baseline to the last visit in the Open-Label Stabilization Period (Week 12), or initiation of additional medications to treat symptoms of TD, or requirement of hospitalization for worsening symptoms of TD in all participants during the Double-Blind R/WD period for ecopipam compared to placebo. The YGTSS was a clinician-completed rating scale used to quantify overall tic severity in children and adults with TD as well as specific subdomains of tic number, frequency, intensity, complexity and interference. Each of these subdomains was scored, on a 0 to 5 scale, separately for motor and vocal tics and then summed across both motor and vocal tics to yield a total tic score ranging from 0 to 50. Higher scores represented more severe symptoms.
Time frame: From randomization at Week 12 through the end of the double-blind R/WD period (up to Week 24)
Population: The mITT Set included all randomized participants who received at least 1 dose of study drug post-randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Double- Blind R/WD Period: Ecopipam 1.8 mg/kg/Day | Time From Randomization to Relapse in All Participants During the Double-Blind R/WD Period | NA weeks |
| Double- Blind R/WD Period: Placebo | Time From Randomization to Relapse in All Participants During the Double-Blind R/WD Period | 4.0 weeks |