Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 5 June 2023
• Main ID: NCT03731715
• Date of registration: 16/10/2018
• Prospective Registration: Yes
• Primary sponsor: SK Life Science, Inc.
• Public title: Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome
• Scientific title: Phase I, Open-Label, Pharmacokinetic, Dose Escalation Study of Carisbamate in Adult and Pediatric Subjects With Lennox-Gastaut Syndrome
• Date of first enrolment: February 7, 2019
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03731715
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Basic Science. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: Marc Kamin, MD
• Affiliation: SK Life Science, Inc.

Key inclusion & exclusion criteria

Inclusion Criteria:

1. Diagnosis of LGS as evidenced by the following:

1. More than 1 type of generalized seizure, including drop seizures (atonic, tonic,
or myoclonic), for =6 months before Visit 1

2. Previous electroencephalogram reporting diagnostic criteria for LGS (abnormal
background activity accompanied by slow spike-and-wave pattern <2.5 Hz)

2. Male or female aged =2 years at the time of consent

3. Aged <11 years at the onset of LGS

4. Written informed consent signed by the subject or legal guardian prior to entering the
study in accordance with the ICH GCP guidelines. Age appropriate assent will be
obtained for children and adolescents. If the written informed consent is provided by
the legal guardian because the subject is unable to do so, a written or verbal assent
from the subject must also be obtained.

5. Receiving 1 to 3 concomitant AEDs at a stable dose for =30 days before Visit 1 (vagal
nerve stimulation [VNS] and ketogenic diet, stable and ongoing for =30 days before
Visit 1, do not count as AEDs)

6. In the Investigator's opinion, parents or caregivers must be able to report accurate
seizure assessments during the screening and study periods and subjects must be able
to ingest study drug

7. Body weight =8 kg for subjects enrolled in Cohort IV

8. Subjects with an implanted vagal nerve stimulator will be allowed if the vagal nerve
stimulator was implanted at least 5 months prior to Visit 1 (Screening) and the
stimulator parameters are not changed for 30 days prior to Visit 1 and for the
duration of the study

9. Subjects following a ketogenic diet will be allowed as long as the diet has been
stable for at least 30 days prior to Visit 1 (Screening) and will remain stable for
the duration of the study.

Exclusion Criteria:

1. Progressive neurological disease

2. Prior treatment with carisbamate

3. Evidence of clinically significant disease or any medical condition that would
compromise the subject's ability to safely complete the study

4. Any surgical or medical condition that may interfere with the absorption,
distribution, metabolism, or excretion of the investigational medicine product

5. Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 days before
Day 1

6. Scheduled for surgery during the study

7. Ketogenic diet or VNS, unless stable and ongoing for =30 days before Visit 1

8. Treatment with an investigational drug or device =30 days before Visit 1

9. Status epilepticus within 12 weeks of Visit 1

10. Felbamate for <1 year (subjects taking felbamate for =1 year must have a stable dose
for 60 days before Visit 1)

11. Concomitant use of vigabatrin or other medications known to be inducers of CYP3A

12. Use of drugs known as UGT inducers, e.g., carbamazepine, phenytoin, phenobarbital,
primidone, or oxcarbazepine

13. Use of cannabinoids (any form), cannabidiols, or medical or recreational marijuana

14. Use of any prescription or non-prescription drugs, including over-the-counter
medication, non-routine vitamins and herbal products within 2 weeks prior to study
drug administration unless discussed and agreed with the Sponsor's medical
representative in writing. (Medication used to treat TEAEs does not lead to a
compulsory exclusion of subjects.)

15. Consumption of any caffeine-containing products (e.g., coffee, tea, chocolate, or
soda) or alcoholic beverages within 48 hours before Day 1 and until the end of each PK
sampling period

16. Consumption of grapefruit or grapefruit-containing products within 72 hours before Day
1 and until the end of each PK sampling period

17. History of any serious drug-induced hypersensitivity reaction (including but not
limited to Stevens Johnson syndrome, toxic epidermal necrolysis, Drug Rash with
Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring
hospitalization

18. History of AED-associated rash that involved conjunctiva or mucosae

19. History of more than one non-serious drug-related hypersensitivity reaction that
required discontinuation of the medication

20. Significant clinical laboratory abnormalities, including elevation of serum AST or ALT
more than 1.5 times ULN for age group, or any elevation of bilirubin or creatinine
about the ULN for age group at Screening

21. Any clinically-significant uncontrolled medical illness, including hepatic or renal
failure, ischemic disease, human immunodeficiency virus (HIV) infection, active
sexually-transmitted disease (STD), active viral hepatitis, malignancy, or any
disorder that in the judgement of the investigator places the subject at risk by
participation in this study

22. History of drug-induced liver injury

23. Positive urine screen of drugs of abuse (if not due to concomitant medication, e.g.
benzodiazepines as hypnotics) for adult and adolescent subjects.

24. Adrenocorticotropic hormone within the 6 months before Visit 1

25. History of anoxic episodes requiring resuscitation within 6 months before Visit 1,
drug or alcohol dependency or abuse within approximately the last 2 years, or use of
illegal recreational drugs

26. Females who are breastfeeding or pregnant at Screening or Baseline or who are of
reproductive age and do not agree to be abstinent or to use highly effective
contraception

27. Intermittent use of benzodiazepine of >4 single administrations in the month before
Visit 1

28. Clinically significant abnormality on the 12-lead ECG at Screening, and any child or
adolescent with a QTcF less than 330 ms or greater than 450 ms

29. Congenital short QT syndrome

30. Hypersensitivity to the study drug or any of the excipients

31. Psychotic disorder(s) or unstable recurrent affective disorder(s)



Age minimum: 2 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Lennox Gastaut Syndrome

Intervention(s)

Drug: Carisbamate

Primary Outcome(s)

The area under the curve (AUC) of carisbamate after a single and multiple doses of carisbamate. [Time Frame: Days 1-3, Day 17]

The maximum plasma concentration (Cmax) after a single and multiple doses of carisbamate. [Time Frame: Days 1-3, Day 17]

Secondary Outcome(s)

Safety - adverse events (AEs) reporting after a single and multiple doses of carisbamate. [Time Frame: Days 1-87]

Secondary ID(s)

YKP509C001

Source(s) of Monetary Support

Please refer to primary and secondary sponsors