Carisbamate in Adult & Pediatric Subjects With Lennox-Gastaut Syndrome

NCT03731715 | Completed Phase 1 FDA Drug

• 1 other identifier: YKP509C001
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open-label, multi-center study of carisbamate in adult and pediatric subjects with LGS, with single- and multiple-dose PK assessments from Days 1 through 73. There will be a Screening Period of up to 28 days and a Treatment Period of 87 days.

Conditions

Lennox Gastaut Syndrome

Keywords

LGS

Outcome Measures

Primary Outcomes (2)

• The area under the curve (AUC) of carisbamate after a single and multiple doses of carisbamate.

  Safety Assessment

  Days 1-3, Day 17

• The maximum plasma concentration (Cmax) after a single and multiple doses of carisbamate.

  Safety assessment

  Days 1-3, Day 17

Secondary Outcomes (1)

• Safety - adverse events (AEs) reporting after a single and multiple doses of carisbamate.

  Days 1-87

Study Arms (4)

Cohort I

EXPERIMENTAL

Subjects ≥18 years of age. Carisbamate, 200 mg, will be administered on Day 1 and 2 of the single-dose period. Carisbamate will be administered at 100 mg twice daily (BID) during the multiple-dose period.

Drug: Carisbamate

Cohort II

EXPERIMENTAL

Subjects 12 to \<18 years of age. Carisbamate, 140 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 70 mg twice daily (BID) during the multiple-dose period.

Drug: Carisbamate

Cohort III

EXPERIMENTAL

Subjects 6 to \<12 years of age. Carisbamate, 60 mg, will be administered on Day 1 and 2 of the single dose period. Carisbamate will be administered at 30 mg twice daily (BID) during the multiple-dose period.

Drug: Carisbamate

Cohort IV

EXPERIMENTAL

Subjects 2 to \<6 years of age. The starting doses for the single dose and multiple-dose periods will be based on the PK and safety results of the first 3 cohorts.

Drug: Carisbamate

Interventions

Carisbamate DRUG

An oral liquid formulation (20 mg/mL) of carisbamate (S-carisbamate)

Also known as: YKP509

Cohort I; Cohort II; Cohort III; Cohort IV

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of LGS as evidenced by the following:
• More than 1 type of generalized seizure, including drop seizures (atonic, tonic, or myoclonic), for ≥6 months before Visit 1
• Previous electroencephalogram reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow spike-and-wave pattern \<2.5 Hz)
• Male or female aged ≥2 years at the time of consent
• Aged \<11 years at the onset of LGS
• 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.
• 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)
• 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
• Body weight ≥8 kg for subjects enrolled in Cohort IV
• 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
• 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.

You may not qualify if:

• Progressive neurological disease
• Prior treatment with carisbamate
• Evidence of clinically significant disease or any medical condition that would compromise the subject's ability to safely complete the study
• Any surgical or medical condition that may interfere with the absorption, distribution, metabolism, or excretion of the investigational medicine product
• Acute disease state (e.g., nausea, vomiting, fever, or diarrhea) within 7 days before Day 1
• Scheduled for surgery during the study
• Ketogenic diet or VNS, unless stable and ongoing for ≥30 days before Visit 1
• Treatment with an investigational drug or device ≥30 days before Visit 1
• Status epilepticus within 12 weeks of Visit 1
• Felbamate for \<1 year (subjects taking felbamate for ≥1 year must have a stable dose for 60 days before Visit 1)
• Concomitant use of vigabatrin or other medications known to be inducers of CYP3A
• Use of drugs known as UGT inducers, e.g., carbamazepine, phenytoin, phenobarbital, primidone, or oxcarbazepine
• Use of cannabinoids (any form), cannabidiols, or medical or recreational marijuana
• 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
• Consumption of grapefruit or grapefruit-containing products within 72 hours before Day 1 and until the end of each PK sampling period

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (7)

Johns Hopkins Hospital

Baltimore, Maryland, 21210, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Duke Health

Durham, North Carolina, 27710, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

The University of Utah School of Medicine - Primary Children's Hospital (Primary Children's Medical Center)

Salt Lake City, Utah, 84113, United States

Location

UW Valley Medical Center

Renton, Washington, 98055, United States

Location

MeSH Terms

Conditions

Lennox Gastaut Syndrome

Interventions

S-2-O-carbamoyl-1-o-chlorophenyl-ethanol

Condition Hierarchy (Ancestors)

Epileptic Syndromes; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Marc Kamin, MD

  SK Life Science, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: November 6, 2018
• Study Start: February 7, 2019
• Primary Completion: May 23, 2022
• Study Completion: June 29, 2022
• Last Updated: May 30, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)