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Purpose

This trial is intended to study the safety and effectiveness of an new anti-epileptic drug (AED) on Primary Generalized Tonic-Clonic (PGTC) Seizures. Eligible Subjects, adults and adolescents, will continue to take their usual AEDs and receive either cenobamate or placebo. Subjects will have a 50% chance or receiving cenobamate or placebo (sugar pill). Subjects will initially receive 12.5 mg of cenobamate or placebo (study drug) and increase the dose every two weeks until they reach a target dose of 200 mg. Subjects will take study drug at approximately the same time in the morning (once a day) with or without food. If tolerability issues arise, dosing can be changed to evening. Also, once a subject reaches 200 mg, the dose can be decreased one time to 150 mg, if necessary. The treatment period is 22 weeks and there is a 3 week follow up period, which includes a one week decrease in study drug to 100 mg prior to stopping. The adolescent subjects will follow the same regimen in an oral suspension adolescent equivalent dose based on weight. Subjects who complete may be eligible for an extension study and will not have to complete the follow up period. Subjects will track their seizure types and frequency in a diary throughout the study.

Condition

Eligibility

Eligible Ages
Over 12 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Subject is male or female and aged ≥12 years. 2. Written informed consent signed by the subject or legal guardian, or legally authorized representative (LAR), prior to entering the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) guidelines. Age- appropriate assent will be obtained for 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. As required by country-specific regulations, only the subject may sign the Informed Consent Form (ICF) in accordance with ICH guidelines. 3. Female subjects of childbearing potential are willing to use an acceptable form of birth control 4. Subject has a clinical diagnosis of PGTC seizures (with or without other subtypes of generalized seizures) in the setting of idiopathic generalized epilepsy. 5. Subject experiences at least 5 PGTC seizures in 12 weeks during the Pre-Randomization Period. 6. Subject has had a routine electroencephalogram (EEG) within 5 years prior to Visit1 (Screening/Baseline) or during the Pre-Randomization Period with electroencephalographic features consistent with idiopathic generalized epilepsy; other concomitant anomalies must be explained by adequate past medical history. 7. Subject has undergone computed tomography (CT) or magnetic resonance imaging (MRI) within 10 years prior to Visit 1 (Screening/Baseline) or during the Pre-Randomization Period that ruled out a progressive cause of epilepsy. 8. Subject is currently receiving 1 to a maximum of 3 concomitant AEDs with fixed dosing regimens for a minimum of 30 days prior to Visit 1 (Screening/Baseline). 1. Benzodiazepines (except diazepam, see Exclusion Criterion No.7) taken at least once per week during the 30 days prior to Visit 1 (Screening/Baseline) for epilepsy, anxiety, or sleep disorder will be counted as 1 AED and the dosage must be continued unchanged throughout the study. Therefore, only a maximum of 2 additional approved AEDs will be allowed. (See Exclusion Criterion No. 10 for intermittent benzodiazepine rescue parameters.) 2. Subjects receiving felbamate as a concomitant AED must meet the following criteria: i. Have a 2-year history of felbamate use and a history of a fixed dosing regimen for a minimum of 60 days prior to Visit 1 (Screening/Baseline). ii. No prior or known history of hepatotoxicity or hematologic disorder due to felbamate. 9. Subject with an implanted vagal nerve or deep brain stimulator will be allowed if the stimulator was implanted at least 5 months prior to Visit 1 (Screening/Baseline) and the stimulator parameters are not changed for 30 days prior to Visit 1 and for the duration of the study. 10. Subject taking a ketogenic diet will be allowed as long as the diet has been stable for at least 3 months prior to Visit 1 (Screening/Baseline) and will remain stable for the duration of the study.

Exclusion Criteria

  1. Female subjects who are pregnant (or planning to become pregnant during the study), lactating, or breast-feeding. 2. Subject has a history o f status epilepticus that required hospitalization within 12 months prior to Visit 1 (Screening/Baseline). 3. Subject has PGTC seizure clusters where individual seizures cannot be counted or classified. 4. Subject has a history of non-epileptic psychogenic seizures. 5. Subject has a concomitant diagnosis of Partial Onset Seizures (POS). 6. Subject has a clinical diagnosis of Lennox-Gastaut syndrome. 7. Subject is currently taking (within the 30 days prior to Visit 1 [Screening/Baseline]) any of the following medications: diazepam (for any reason other than as intermittent benzodiazepine rescue medication), phenytoin, mephenytoin, fosphenytoin, phenobarbital, primidone, ethotoin, clopidogrel, fluvoxamine, amitriptyline, clomipramine, bupropion, methadone, ifosfamide, cyclophosphamide, or efavirenz. 8. Subject has participated in previous cenobamate clinical studies. 9. Subject has a history of vigabatrin use within 5months prior to Visit 1 (Screening/Baseline), or the subject plans to begin treatment with vigabatrin during the study. a) A subject with a history of vigabatrin use that ended more than 5 months prior to Visit1 may be enrolled after documented evidence of no vigabatrin-associated clinically significant abnormality in an automated visual perimetry test. 10. Subject has a history of intermittent use of rescue benzodiazepines (i.e., 1 to 2 doses over a 24-hour period is considered a 1-time rescue) 4 or more times within the 30 days prior to Visit 1 (Screening/Baseline). 11. Subject has received an investigational drug or device within 30 days prior to Visit 1 (Screening/Baseline). 12. Subject has a history of drug or alcohol dependency or abuse within 2 years prior to Visit 1 (Screening/Baseline). 13. Subject tests positive, via urine drug screen at Visit 1 (Screening/Baseline), for illicit drugs not legalized in your region/state, or for a drug that has not been prescribed (e.g., certain opiates). 14. Subject has a history of any serious drug-induced hypersensitivity reaction (including, but not limited to, Stevens Johnson syndrome, toxic epidermal necrolysis, or DRESS) or any drug-related rash requiring hospitalization. 15. History of AED-associated rash that involved conjunctiva or mucosae. 16. History of more than one non-serious drug-related hypersensitivity reaction that required discontinuation of the medication. 17. Subject has evidence of clinically significant abnormalities or disease (e.g., psychiatric, cardiac, respiratory, gastrointestinal, hepatic [aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 2 times the upper limit of normal (ULN), or total or direct bilirubin not more than ULN], or renal disease) that, in the opinion of the Principal Investigator, could affect the subject's safety or conduct of the study. 18. Presence of congenital short QT syndrome or relevant replicated change in QT/QTc interval less than 340 msec on ECG. 19. Subject has any significant active Central Nervous System (CNS) infection, demyelinating disease, degenerative neurologic disease or any CNS disease deemed to be progressive during the course of the study that may confound the interpretation of the study results. 20. Subject has a creatinine clearance less than 50 mL/min, as calculated by Cockcroft-Gault equation. 21. Subject has an absolute neutrophil count less than 1500/µL. 22. Subject has platelet count lower than 80,000/µL in subjects treated with valproate. 23. Subject has a history of positive antibody/antigen test for hepatitis A, hepatitis B, hepatitis C, or HIV. 24. Subject has any suicidal ideation (with intent with or without a plan) at Visit 1 (Screening/Baseline) or Visit 4 (Randomization) (i.e., answering YES to Question 4 and/or Question 5 on the Suicidal Ideation section of the C-SSRS). 25. Subject has more than 1 lifetime suicide attempt. 26. Subject is a staff member or immediate family member of study staff. 27. Previous exposure to cenobamate or sensitivity/allergy to components of the oral suspension. Any potential exception to the inclusion as well as exclusion criteria allowing de minimis (clinically trivial and meaningless) variations must be approved by the Medical Monitor.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cenobamate
Cenobamate 12.5 mg tablet once a day for two weeks, 25 mg tablet once a day for two weeks, 50 mg tablet once a day for two weeks, 100 mg tablets once a day for two weeks, 150 mg tablets once a day for two weeks and 200 mg tablets once a day for twelve weeks. The adolescent subjects will follow the same regimen in an oral suspension adolescent equivalent dose based on weight.
  • Drug: Cenobamate
    12.5 mg tablet, 25 mg tablet, 50 mg tablet, 100 mg tablets, 150 mg tablets, 200 mg tablets. The adolescent subjects will follow the same regimen in an oral suspension adolescent equivalent dose based on weight.
    Other names:
    • YKP3089
Placebo Comparator
Placebo
Matching placebo
  • Drug: Placebo
    Matching Placebo
    Other names:
    • PBO

Recruiting Locations

Phoenix Children's Hospital
Phoenix, Arizona 85016

Northeast Regional Epilepsy Group
Hackensack, New Jersey 07601

ANRC Research
El Paso, Texas 79912

Child Neurology Consultants of Austin
Austin, Texas 78757

LeBonheur Children's Medical Center
Memphis, Tennessee 38105

University of Toledo
Toledo, Ohio 43606

Duke University Children's Health Center
Durham, North Carolina 27710

Saint Peter's University Hospital
New Brunswick, New Jersey 08901

University of Missouri Health Care
Columbia, Missouri 65201

Center for Neurosciences
Tucson, Arizona 85718

Minneapolis Clinic of Neurology Golden Valley
Golden Valley, Minnesota 55422

Mid-Atlantic Epilepsy and Sleep Center
Bethesda, Maryland 20817

Rush University
Chicago, Illinois 60612

Children's Healthcare of Atlanta
Atlanta, Georgia 30329

Clinical Integrative Research Center of Atlanta, CIRCA
Atlanta, Georgia 30328

University of South Florida
Tampa, Florida 33606

Children's Hospital of Colorado
Grand Junction, Colorado 80045

University of Utah / Primary Children's Hospital
Salt Lake City, Utah 84113

More Details

NCT ID
NCT03678753
Status
Recruiting
Sponsor
SK Life Science, Inc.

Study Contact

Sunita Misra, MD
1-402-835-5977
smisra@sklsi.com

Detailed Description

This randomized, double-blind, placebo controlled trial is designed to evaluate safety, efficacy, and pharmacokinetics of cenobamate adjunctive therapy as compared to placebo on PGTC seizures in subject with idiopathic generalized epilepsy. Subjects will be randomized to receive either cenobamate or placebo on a 1:1 basis. The study will have three periods, pre-randomization period where a baseline seizure frequency is established, treatment period and follow up period. The treatment period consists of a 10 week titration phase where subjects are titrated slowly until they reach the target dose and a maintenance phase. During the titration phase, subjects will receive 12.5 mg study drug, followed by 25 mg, 50 mg, 100 mg, and 150 mg study drug every two weeks. During the maintenance phase, subjects will receive the target dose of 200 mg study drug or adolescent equivalent. Subjects will take their once daily dose of study drug at approximately the same in the morning with or without food. If tolerability issues arise, subjects can switch to evening dosing. There is also an option to down-titrate to 150 mg study drug, one time only. If tolerability issues continue, subjects may be discontinued. Upon completion of the maintenance phase, eligible subjects will have an opportunity to enroll in an open-label safety study. Subjects who discontinue early or do not wish to participate in this additional study will complete the three week follow up period. Subjects may receive a one week down titration to 100 mg and return for a follow up visit 2 weeks later. The adolescent subjects will follow the same regimen in an oral suspension adolescent equivalent dose based on weight. Throughout the study, subjects will keep a diary containing the type and frequency of seizures. This will be the primary efficacy measure.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.