Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
Subject must have a documented history of Lennox-Gastaut syndrome by:
1. Evidence of more than one type of seizure, of which at least one should be an
atonic or tonic seizure.
2. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS
(abnormal background activity accompanied by slow, spike and wave pattern <3.0
Hz).
3. History of developmental delay.
2. Male or female subjects.
3. Subjects must be age 4-55 years at the time of consent/assent.
4. Must have been < 11 years old at the onset of LGS.
5. Subjects must have experienced at least 2 drop seizures with potential to fall (tonic,
atonic, tonic-clonic) each week during the 4-week Baseline period preceding
randomization. Drop seizures are defined as a seizure involving the entire body,
trunk, or head that led or could have led to a fall, injury, slumping in a chair, or
hitting the subject's head on a surface. For seizures that occur in clusters: if
countable, an exact seizure count should be used; if uncountable, the caregiver should
estimate the number of seizures.
6. Subjects must have been receiving 1 to 4 concomitant anti-seizure medications (ASMs)
at a stable dose for at least 4 weeks before Visit 1.
7. If not taking Epidiolex, subjects may take other approved cannabidiol or over the
counter cannabidiol products. If taking cannabidiol other than Epidiolex, consult
Medical Monitor to determine if it counts as a concomitant ASM.
8. Dietary therapy and any CNS stimulator settings must be stable for 4 weeks prior to
baseline and maintain stable regimen throughout the study. The dietary therapy and CNS
stimulators are not counted as an ASM.
9. Parents or caregivers must be able to keep accurate seizure diaries.
10. Subject is either not of childbearing potential, defined as premenarchal,
postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation,
bilateral oophorectomy, or hysterectomy), if of childbearing potential, must comply
with an acceptable method of birth control during the study, for at least 4 weeks
prior to study entry and for 4 weeks following completion of the study, if able.
11. Subject and/or parent(s)/legal representative must be willing and able to give
informed assent/consent for participation in the study.
12. Subject and their caregiver must be willing and able (in the investigator's opinion)
to comply with all study requirements.
13. History of COVID-19 vaccination is permitted.
Exclusion Criteria:
1. Etiology of subject's seizures is a progressive neurologic disease. Subjects with
tuberous sclerosis will not be excluded from study participation, unless there is a
progressive brain tumor.
2. Evidence of clinically significant disease (e.g., cardiac, respiratory,
gastrointestinal, renal disease, hepatic disease) that in the opinion of the
investigator(s) could affect the subject's safety or study conduct.
3. Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior
to baseline.
4. Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or
suffers from frequent stooling.
5. Current use of felbamate with less than 18 months of continuous exposure.
6. Concomitant use of vigabatrin: subjects who took vigabatrin in the past must be
discontinued for at least 5 months before Visit 1 and must have documentation showing
no evidence of a vigabatrin-associated clinically significant abnormality in an
automated visual perimetry test, if able.
7. Subject who had a history of hypoxia which needed emergency resuscitation within 12
months prior to baseline.
8. Status epilepticus within 12 weeks of Visit 1.
9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit
1, as determined by the Investigator.
10. Subject has clinically significant abnormal laboratory values, in the investigator's
opinion, at Visit 1 or time of randomization (Visit 2).
11. Subject has a history of any serious drug-induced hypersensitivity, e.g., toxic
epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms
[DRESS]) or any drug-related rash requiring hospitalization.
12. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive
Neurostimulator System (RNS) or other neurostimulation for epilepsy device implanted
or activated < 5 months year prior to enrollment. Stimulation parameters that have been
stable for < 4 weeks, or Battery life of unit not anticipated to extend for duration of
trial.
13. Subject is pregnant, may be pregnant, lactating or planning to be pregnant.
14. Any suicidal ideation with intent, with or without a plan within 6 months before Visit
2 (i.e., answering "Yes" to questions 4 or 5 in the Suicidal Ideation section of the
age- specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and
above who are able to be evaluated.
15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any
question in the Suicidal behavior section of the age-specific Columbia-Suicide
Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be
evaluated.
16. Evidence of significant active hepatic disease. Stable elevations of liver enzymes
(alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) due to
concomitant medication(s) will be allowed if they are < 3 x ULN.
17. Subject with total bilirubin [TBL] > 2 x ULN (except for Gilbert's syndrome).
18. Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening
visit (Visit 1).
19. History of positive antibody/antigen test for human immunodeficiency virus (HIV).
20. If taking Epidiolex, subject may not use other approved cannabidiol or over the
counter cannabidiol products.
21. Scheduled for epilepsy-related surgery, VNS insertion, or any other
stimulators/surgery during the projected course of the study.
22. Subject who has taken or used any investigational drug or device in the 4 weeks prior
to the screening visit (Visit 1).
23. Concomitant use of medications known to be strong inducers of cytochrome P450 (CYP3A)
including, but not limited to: phenobarbital, phenytoin, carbamazepine, primidone,
rifampin, troglitazone, St. John's Wort, efavirenz, nevirapine, glucocorticoids (other
than topical usage), modafinil, pioglitazone, and rifabutin.
24. Evidence of cardiac disease, including unstable angina, myocardial infarction, within
the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT.
syndrome
25. Subject with a short QTc interval (< 340 msec) or long QTc interval (> 460 msec) as
confirmed by a repeated electrocardiogram (ECG).
26. Benzodiazepine rescue administered on average more than once a week in the month
before Visit 1.
27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral
suspension.
Note: Other protocol defined Inclusion/Exclusion Criteria may apply.
Eligibility last updated 7/28/22. Questions regarding updates should be directed to the study team contact.