Investigate Efficacy and Safety of Carisbamate as Adjunctive Treatment for Seizures Associated With LGS in Children and Adults

Launched by SK LIFE SCIENCE, INC. · Jan 20, 2022

Keywords

ClinConnect Summary

This clinical trial is studying the medication carisbamate to see if it can help reduce the number of drop seizures in children and adults with Lennox-Gastaut Syndrome (LGS). LGS is a type of epilepsy characterized by different seizure types, including drop seizures, which can cause a person to fall unexpectedly. The trial is open to both children and adults aged 4 to 55 who have been diagnosed with LGS and have experienced at least two drop seizures in the month before starting the study. Participants must also be taking one to four other seizure medications that have been stable for at least four weeks.

If you or your loved one joins the study, you can expect to take either carisbamate or a placebo (a non-active treatment) for a set period. Throughout the trial, caregivers will need to keep track of seizure activity in a diary. This study aims to determine if carisbamate is an effective and safe option for managing seizures in individuals with LGS. It’s important to note that there are specific eligibility requirements, and potential participants should discuss these with their healthcare provider to see if they qualify.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• 1. 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) during the 4-week Baseline period preceding randomization (minimum of 4 drop seizures in the first two weeks and 4 in the last two weeks). 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. All drop seizure types must be countable (either as isolated seizures or as countable isolated seizures in a cluster).
• • 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 caregiver(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 prior to Visit 1
• • 9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated 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.