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

Recruiting

Trial ID: NCT05219617

Purpose

The primary objective is to evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the number of drop seizures (tonic, atonic, and tonic-clonic) compared with placebo in pediatric and adult subjects (age 4-55 years) diagnosed with Lennox Gastaut Syndrome (LGS).

Official Title

A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults, With Optional Open-Label Extension

Stanford Investigator(s)

Eligibility


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.

Intervention(s):

drug: Carisbamate

Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305