The goal of this expanded access study is to learn about the long-term effects ofEcopipam in participants with Tourette's Disorder (TD). The main question it aims toanswer is: - Is ecopipam safe and well-tolerated in participants equal and over the age of 6 to 50 with TD? - Assess quality of life measures and to provide access to ecopipam while NDA is being prepared and submitted for review for marketing approvalEligible participants with TD will take ecopipam with guidance from their treatingphysician. In addition to the standard of care from the treating physician, treatmentwith ecopipam will continue until ecopipam becomes commercially available in the UnitedStates or the program is terminated.While in the EAP program, participants will be asked regarding how safe and tolerableecopipam is to the participant. Several questionnaires will be collected regardingparticipants experiences while taking ecopipam during monthly visits for the first yearand every three months thereafter until the conclusion of the study.
The main purpose of this study is to further study the safety and tolerability of
ecopipam in children, adolescents, and adults with Tourette's Disorder (TD).
The secondary objectives of this program are to assess patient-reported outcome measures
including quality of life (QOL) and to provide access to ecopipam while a U.S. New Drug
Application (NDA) is being prepared and submitted for review for marketing approval in
the U.S.
This is an open label expanded access program for ecopipam (EBS-101) intended to collect
safety information and physician-administered psychiatric scales and patient-reported
outcomes in children, adolescents, and adults in the U.S. with TD who are unable to take
currently approved medications for TD (aripiprazole, haloperidol, or pimozide) or any
other D2 receptor antagonists (D2rA) due to treatment failure, intolerability, safety or
lack of access.
At the Screening visit, participants will provide informed consent [adult participants or
children/adolescent Legally Acceptable Representative (LAR)] and assent
(children/adolescents) and be assessed against the inclusion/exclusion criteria for
participation in the study. Demographic information, disease comorbidities, and
concomitant medications will be documented, vital signs and a physical examination will
be performed, blood and urine samples will be collected for safety laboratories, an
electrocardiogram (ECG) will be performed, lifetime history for suicidality will be
assessed using the Columbia Suicidality Severity Rating Scale (C-SSRS), and age group
validated scales to assess anxiety and depression will be performed. The participant and
in the case of pediatric participants their LAR will also be asked to complete scales to
assess the severity of their disease and quality of life.
Based on satisfying Screening visit criteria, participants will receive a telephone call
to confirm Enrollment (Day 1). Visit dates will be defined from date of first dose. Once
Enrollment is confirmed, eligible participants will be registered with a specialty
pharmacy who will dispense ecopipam. Participants will be gradually titrated over a
period of 2-4 weeks depending on their weight to achieve a target steady-state dose of
1.8 mg/kg/day ecopipam (2 mg/kg/day ecopipam HCl).
Following the Enrollment call, there will be a telemedicine assessment in approximately 2
weeks to assess adverse events (AEs) and participant tolerance to ecopipam. Participants
will return to the clinic at monthly intervals for safety and efficacy assessments for
the first year of treatment and every 3 months thereafter until study termination as
outlined in the Schedule of Assessments (Table 5).
Participants will also be contacted 30 days after the last dose of study drug to
determine any additional AEs or concomitant medications, to administer the C-SSRS and to
confirm compliance with taper down medication and study drug return.
Drug: ecopipam HCl ~2mg/kg/day
Daily oral tablet taken every evening before bedtime.
Other Name: EBS-101
Participants must fulfill all of the following inclusion criteria to be eligible for
participation in the Study:
1. Age 6 to 50 years old inclusive at the time of informed consent/assent.
2. Participant must sign/date the most current Informed Consent Form (ICF). For minor
participants the LAR must/sign date the most current consent and the participant
must sign/date the most current age-appropriate assent.
3. In the opinion of the principal investigator (PI), the participant or in the case of
a minor their LAR is capable of understanding and complying with protocol and
program requirements, oral drug administration and care instructions.
4. Weight ≥18 kg (39.6 lbs.).
5. In the opinion of the PI, the participant meets diagnostic criteria for Tourette's
Syndrome (TS) per Diagnostic and Statistical manual for Mental Disorders - 5th
Edition (DSM-5-TR diagnostic criteria for TD).
6. The participant must have been treated with an FDA-approved treatment for TD
(aripiprazole, haloperidol, or pimozide) or any other D2r antagonist (D2rA) and have
experienced treatment failure, tolerability or safety issues as per LAR, participant
or prescribing clinician or not have access to any of these approved medications.
7. Females of child-bearing potential must have a negative urine pregnancy test at
Screening.
8. Females of child-bearing potential who are sexually active or become sexually active
must be using double barrier method (condom and IUD, condom and spermicide, etc.) in
addition to any oral contraceptive they may be using and agree to continue use of
double barrier contraception for the duration of their participation in the study
and for 30 days after their last dose of study drug. Females of non-childbearing
potential are exempt from this criterion.
Non-Childbearing potential is defined by:
1. Post menopausal defined as >= 2 years amenorrheic, or,
2. Bilateral salpingo-oopherectomy, or
3. Hysterectomy, or
4. Pre-menarche
9. Sexually active male participants 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.
10. Male participants must agree to not donate sperm and female participants not to
donate eggs for at least 30 days after the last dose of study drug.
Diagnosis and Main Criteria for Inclusion:
Inclusion Criteria
Participants must fulfill all of the following inclusion criteria to be eligible for
participation in the Study:
1. Age 6 to 50 years old inclusive at the time of informed consent/assent.
2. Participant must sign/date the most current Informed Consent Form (ICF). For minor
participants the LAR must/sign date the most current consent and the participant
must sign/date the most current age-appropriate assent.
3. In the opinion of the principal investigator (PI), the participant or in the case of
a minor their LAR is capable of understanding and complying with protocol and
program requirements, oral drug administration and care instructions.
4. Weight ≥18 kg (39.6 lbs.).
5. In the opinion of the PI, the participant meets diagnostic criteria for Tourette's
Syndrome (TS) per Diagnostic and Statistical manual for Mental Disorders - 5th
Edition (DSM-5-TR diagnostic criteria for TD).
6. The participant must have been treated with an FDA-approved treatment for TD
(aripiprazole, haloperidol, or pimozide) or any other D2r antagonist (D2rA) and have
experienced treatment failure, tolerability or safety issues as per LAR, participant
or prescribing clinician or not have access to any of these approved medications.
7. Females of child-bearing potential must have a negative urine pregnancy test at
Screening.
8. Females of child-bearing potential who are sexually active or become sexually active
must be using double barrier method (condom and IUD, condom and spermicide, etc.) in
addition to any oral contraceptive they may be using and agree to continue use of
double barrier contraception for the duration of their participation in the study
and for 30 days after their last dose of study drug. Females of non-childbearing
potential are exempt from this criterion.
Non-Childbearing potential is defined by:
1. Post menopausal defined as >= 2 years amenorrheic, or,
2. Bilateral salpingo-oopherectomy, or
3. Hysterectomy, or
4. Pre-menarche
9. Sexually active male participants 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.
10. Male participants must agree to not donate sperm and female participants not to
donate eggs for at least 30 days after the last dose of study drug.
Participants cannot be enrolled in the study if they meet any of the following criteria.
1. Clinically meaningful abnormalities on laboratory tests at Screening as determined
by the PI.
2. Specific laboratory findings at enrollment
1. T. Bili >= 2.5 x ULN for age (Participants with a history of Gilbert's Disorder
must have prior documentation of the disorder.)
2. ALT >= 2.5 x ULN for age
3. AST >= 2.5 x ULN for age
4. Positive urine drug screen for cocaine, amphetamine, benzodiazepines,
barbiturates, phencyclidine (PCP), or opiates at Screening, except those
receiving stable, prescribed treatment for attention deficit/hyperactivity
disorder (ADHD) or a positive for benzodiazepine prescribed (either routine or
as needed) for any anxiety disorder or anxiety associated with a depressive
disorder
5. Severe renal impairment or end stage renal disease as defined by eGFR < 60
ml/min/1.73m2
3. Any of the following cardiovascular:
1. ECG with a QTcF > 450 for males or > 470 for females at screening.
2. A history or finding on the screening ECG of any significant arrhythmia in the
opinion of the principal investigator
3. A known family history of QT prolongation syndrome with sudden death
4. Current or anticipated need for medications known to prolong the QT interval
4. A lifetime history of any of the following disorders:
1. Myocardial Infarction
2. Cancer (excluding Basal Cell Carcinoma or Cervical Cancer in situ)
3. Seizure Disorder (except febrile seizure)
4. Neuroleptic Malignant Syndrome
5. Tardive Dyskinesia
6. Parkinson's Disorder
7. Dementia
8. Essential Tremor
9. Substance Use Disorders (as defined by DSM-5-TR) in the past 6 months prior to
screening. (Excluding nicotine and/or caffeine)
10. Any general medical disorders OR psychiatric disorder that are not under good
control in the opinion of the PI OR require treatment with any prohibited
medication.
5. All prescription or over-the-counter drug (e.g., St. Johns Wort) that are strong and
moderate inhibitors or inducers of CYP3A4; drugs that are substrates of CYP2D6; or
drugs that are substrates of MATE-2K transporters (e.g., metformin).
6. At significant risk of attempting suicide in the opinion of the PI or any one of the
following:
1. A history of a suicide attempt OR behavior in the past one year prior to
Screening.
2. A lifetime history of 2 or more suicide attempts OR behaviors.
3. A history of non-suicidal self-injurious behavior in the past 2 years prior to
Screening.
4. A history of suicide ideation OR thoughts in the past 6 months prior to
Screening.
7. Female participants who are currently pregnant or lactating or planning to become
pregnant during the study.
8. A history of hypersensitivity or allergic reaction to ecopipam or any inactive
ingredient of the formulation.
9. Participants unable to swallow tablets.
10. Any participant who in the opinion of the PI or the Sponsor is not a suitable
candidate for the program.
Cortica Glendale
Glendale, California, United States
Cortica Marin
San Rafael, California, United States
Yale Child Study Center
New Haven, Connecticut, United States
Parkinson's Center of Boca Raton
Boca Raton, Florida, United States
University of Miami
Miami, Florida, United States
Belkis Delgado, MD, PA
Miami, Florida, United States
University of South Florida
St. Petersburg, Florida, United States
Northwestern University
Chicago, Illinois, United States
University of Chicago (Pritzker)
Chicago, Illinois, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Boston Children's Hospital
Boston, Massachusetts, United States
University of Massachusetts- Memorial Health
Worcester, Massachusetts, United States
Neurobehavioral Medicine Group
Bloomfield Hills, Michigan, United States
Stony Brook Medicine
Stony Brook, New York, United States
Cincinnati Children's Hospital
Cincinnati, Ohio, United States
North Star Medical Research, LLC
Middleburg Heights, Ohio, United States
Access Clinical Trials, INC
Nashville, Tennessee, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
BCM-Texas Children's Hospital
Houston, Texas, United States
Medical Affairs Emalex
312-847-1364
medicalaffairs@emalexbiosciences.com
Sarah Atkinson, MD, Study Director
Emalex Biosciences