Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Cenobamate Adjunctive Therapy in PGTC Seizures

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Cenobamate Adjunctive Therapy in Subjects With PGTC Seizures

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. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension 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.

Study Overview

• Status: Recruiting
• Conditions: Primary Generalized Epilepsy
• Intervention / Treatment: Drug: Placebo; Drug: Cenobamate

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. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension 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.

• Study Type: Interventional
• Enrollment (Estimated): 170
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Sunita Misra, MD; Phone Number: 1-402-835-5977; Email: smisra@sklsi.com
• Study Contact Backup: Name: Denise Bonhomme; Phone Number: 1-201-421-3878; Email: dbonhomme@sklsi.com

Study Locations

• Australia
  • Heidelberg, Australia, 3084
    • Recruiting
    • Austin Health
  • South Brisbane, Australia, 4101
    • Recruiting
    • Children's Health Queensland Hospital
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Completed
    • Multiprofile Hospital for Active Treatment Puls AD
  • Ruse, Bulgaria, 7002
    • Completed
    • UMHAT Kanev AD
  • Sofia, Bulgaria, 1336
    • Completed
    • MHAT Lyulin EAD
  • Sofia, Bulgaria, 1407
    • Completed
    • Acibadem City Clinic MHAT Tokuda EAD
  • Sofia, Bulgaria, 1408
    • Completed
    • Diagnostic Consultative Center Neoclinic EAD
  • Varna, Bulgaria, 9000
    • Completed
    • Diagnostic Consultative Center Equita EOOD
  • Veliko Tarnovo, Bulgaria, 5000
    • Completed
    • Medical Center Medica Plus OOD
  • Veliko Tarnovo
    • Gorna Oryahovitsa, Veliko Tarnovo, Bulgaria, 5100
      • Completed
      • MHAT Sv. Ivan Rilski Gorna Oryahovitsa EOOD
• Czechia
  • Brno, Czechia, 656 91
    • Completed
    • Fakultni nemocnice u sv. Anny v Brne, 1. Neurologicka klinika
  • Hradec Králové, Czechia, 500 03
    • Completed
    • Nestatni zdravotnicke zarizeni, privatni ordinance neurologie
  • Ostrava-Poruba, Czechia, 708 52
    • Completed
    • Cerebrovaskularni poradna, s.r.o.
  • Ostrava-Vitkovice, Czechia, 703 00
    • Completed
    • Cerebovaskularni poradna s.r.o.
  • Praha 6, Czechia, 160 00
    • Completed
    • Forbeli s.r.o., Neurologicka ordinace
  • Rychnov Nad Kněžnou, Czechia, 516 01
    • Completed
    • Vestra Clinics, s.r.o.
  • Zlín, Czechia, 760 01
    • Completed
    • Neurologicka ambulance MUDr.Monika Zahumenska
  • Praha
    • Praha 5, Praha, Czechia, 150 06
      • Completed
      • Fakultni nemocnice v Motole
• Germany
  • Berlin, Germany, 13353
    • Recruiting
    • Charite - Universitätsmedizin Berlin - Sozialpädiatrisches Zentrum
  • Jena, Germany
    • Recruiting
    • Universitätsklinikum Jena
  • Kiel, Germany, 24105
    • Recruiting
    • Universitätsklinikum Schleswig-Holstein - Campus Kiel
  • Radeberg, Germany, 01454
    • Recruiting
    • Sächsisches Epilepsiezentrum Kleinwachau gGmbH
• Hungary
  • Budapest, Hungary, 1083
    • Recruiting
    • Semmelweis Egyetem
  • Debrecen, Hungary
    • Recruiting
    • Debreceni Egyetem Klinikai Központ, Gyermekgyógyászati Intézet Nagyerdei krt. 98
  • Hodmezovasarhely, Hungary, 6800
    • Completed
    • Csongrád Megyei Egészségügyi Elláto Központ Ideggyógyászati Osztály
• Korea, Republic of
  • Daegu, Korea, Republic of
    • Withdrawn
    • Keimyung University Dongsan Hospital
  • Suwon, Korea, Republic of
    • Recruiting
    • Ajou University Hospital
  • Chungcheongbuk-Do
    • Cheongju-si, Chungcheongbuk-Do, Korea, Republic of
      • Recruiting
      • Chungbuk National University Hospital
  • Gyeonggi-Do
    • Seoul, Gyeonggi-Do, Korea, Republic of
      • Recruiting
      • SMG-SNU Boramae Medical Center
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of
      • Recruiting
      • CHA Bundang Medical Center
• Poland
  • Dolnoslaskie
    • Tyniec Mały, Dolnoslaskie, Poland, 55-040
      • Completed
      • NZOZ Poradnia Zdrowia Psychicznego Antonijczuk Boleslaw
    • Wrocław, Dolnoslaskie, Poland, 52-416
      • Completed
      • Centrum Medyczne Oporow
  • Iodzkie
    • Ksawerow, Iodzkie, Poland, 95-054
      • Completed
      • Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska S.J.
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-090
      • Completed
      • Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie
  • Malopolskie
    • Krakow, Malopolskie, Poland
      • Recruiting
      • Centrum Medyczne PLEJADY
    • Krakow, Malopolskie, Poland
      • Recruiting
      • Wojewódzki Specjalistyczny Szpital Dziecięcy im. sw. Ludwika sw Krakowie
    • Kraków, Malopolskie, Poland, 31-209
      • Completed
      • Centrum Leczenia Padaczki i Migreny
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-868
      • Completed
      • Centrum Medyczne Warszawa Pratia s.a
  • Silesia
    • Katowice, Silesia, Poland, 40-635
      • Completed
      • Gornoslaskie Centrum Medyczne - Samodzielny Publiczny Szpital Kliniczny Number 7
  • Slaskie
    • Katowice, Slaskie, Poland, 40-081
      • Completed
      • Centrum Medyczne Pratia Katowice
    • Katowice, Slaskie, Poland, 40-571
      • Completed
      • M.A. LEK A.M. Maciejowscy S.C Centrum Terapii SM
    • Katowice, Slaskie, Poland, 40-650
      • Completed
      • Niepubliczny Zaklad Opieki Zdrowotnej Novo-Med
    • Katowice, Slaskie, Poland, 40-851
      • Completed
      • Gyncentrum Clinic Sp. z.o.o
  • Swietokrzyskie
    • Kielce, Swietokrzyskie, Poland
      • Recruiting
      • Niepubliczny Zakład Opieki Zdrowotnej - Centrum Neurologii Dziecięcej i Leczenia Padaczki
      • Contact: Centrum M Plejady
  • Warminsko-Mazurskie
    • Olsztyn, Warminsko-Mazurskie, Poland, 10-561
      • Completed
      • Wojewódzki Szpital Specjalistyczny w Olsztynie
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-848
      • Completed
      • Clinical Research Center Spolka z Ograniczona Odpowiedzialnoscia Medic-R sp. k
• Slovakia
  • Banská Bystrica, Slovakia, 974 04
    • Completed
    • MUDr. Beata Dupejova, neurologická ambulncia, s.r.o
  • Bardejov, Slovakia, 085 01
    • Recruiting
    • IN MEDIC s.r.o
  • Bratislava, Slovakia
    • Recruiting
    • Narodny ustav detskych chorob
  • Dolný Kubín, Slovakia, 026 01
    • Completed
    • MEDBAJ, s.r.o., Neurologicka ambulancia, Nemocnicna 1944/10
  • Krompachy, Slovakia, 053 42
    • Completed
    • NEURES, s.r.o.-Neurologická Ambulancia
  • Trencin
    • Dubnica Nad Váhom, Trencin, Slovakia, 018 41
      • Recruiting
      • Konzílium, s.r.o
• Spain
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
  • Malaga, Spain, 29011
    • Recruiting
    • Hospital Regional Universitario de Málaga
  • Valencia, Spain, 46026
    • Recruiting
    • Hospital Universitario La Fe
• Ukraine
  • Dnipropetrovsk, Ukraine, 49005
    • Completed
    • Communal Enterprise Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov of Dnipropetrovsk Regional Council
  • Ivano-Frankivsk, Ukraine, 76011
    • Completed
    • Municipal Non-profit Enterprise Prykarpattia Regional Clinical Center for Mental Health of Ivano-Frankivsk Regional Council
  • Kharkiv, Ukraine, 61068
    • Completed
    • Communal Non-Commercial Enterprise of Kharkiv Regional Council Regional Clinical Psychiatric Hospital #3
  • Lviv, Ukraine, 79010
    • Completed
    • Communal Non-Profit Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital, Neurological Department, Antiepileptic Center
  • Odessa, Ukraine, 67513
    • Completed
    • Communal Non-Profit Enterprise Odesa Regional Medical Centre of Mental Health Odesa Regional Council, Department #2
  • Odessa, Ukraine, 67513
    • Completed
    • Odessa Regional Psychiatric Hospital No. 2,
  • Poltava, Ukraine, 36000
    • Completed
    • Communal Enterprise Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev of Poltava Regional Council
  • Ternopil, Ukraine, 46020
    • Completed
    • Municipal Non-Profit Enterprise Ternopil Regional Clinical Psychoneurological Hospital of Ternopil Regional Council, Department of Neurology #2
  • Vinnytsya, Ukraine, 21005
    • Completed
    • Municipal Non-profit Enterprise Vinnytsia Regional Clinical Psychoneurological Hospital named after Acad. O.I. Yushchenko of Vinnytsia Regional Council, Department of Neurology #3
  • Dnipro
    • Dnepropetrovsk, Dnipro, Ukraine, 49005
      • Completed
      • Communal Enterprise Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov of Dnipropetrovsk Regional Council, Regional Center of Psychosomatic Disorders based on Psychoneurology Department
  • Dnipropetrovsk
    • Dnipro, Dnipropetrovsk, Ukraine, 49069
      • Completed
      • Municipal Non-profit Enterprise City Clinical Hospital No.16 of Dnipro City Council, Department of Neurology
  • Kyiv
    • Kiev, Kyiv, Ukraine, 02192
      • Completed
      • Kyiv City Psychoneurological Hospital №2
  • Odessa
    • Odesa, Odessa, Ukraine, 65025
      • Completed
      • Municipal Non-Profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council, Department of Cerebro-Vascular Diseases with Neurosurgery
  • Zakarpattia
    • Uzhgorod, Zakarpattia, Ukraine, 88018
      • Completed
      • Municipal Non-profit Enterprise Regional Clinical Center of Neurosurgery and Neurology of Zakarpattia Regional Council, Department of Neurosurgery #2
  • Zaporizhzhya
    • Zaporozhye, Zaporizhzhya, Ukraine, 69600
      • Completed
      • Municipal Non-Profit Enterprise Zaporizhzhia Regional Clinical Hospital Of Zaporizhzhia Regional Council
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Recruiting
      • Phoenix Children's Hospital
    • Tucson, Arizona, United States, 85718
      • Recruiting
      • Center for Neurosciences
  • California
    • Fresno, California, United States, 93710
      • Completed
      • Neuro Pain Medical Center
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • Completed
      • Colorado Springs Neurological Associates
    • Grand Junction, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital of Colorado
  • Florida
    • Miami, Florida, United States, 33176
      • Completed
      • Brainstorm Research
    • Orlando, Florida, United States, 32803
      • Completed
      • Florida Hospital Medical Group
    • Tampa, Florida, United States, 33606
      • Recruiting
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • Clinical Integrative Research Center of Atlanta, CIRCA
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Completed
      • Hawaii Pacific Neuroscience
  • Idaho
    • Boise, Idaho, United States, 83702
      • Completed
      • Consultants in Epilepsy and Neurology
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Rush University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Completed
      • Indiana University
  • Iowa
    • Ames, Iowa, United States, 50010
      • Completed
      • PMG Research of McFarland Clinic
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Completed
      • University of Kentucky
  • Maine
    • Scarborough, Maine, United States, 04074
      • Completed
      • Maine Medical Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Recruiting
      • Mid-Atlantic Epilepsy and Sleep Center
  • Michigan
    • East Lansing, Michigan, United States, 48824
      • Completed
      • Michigan State University
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Completed
      • Minneapolis Clinic of Neurology Golden Valley
  • Missouri
    • Columbia, Missouri, United States, 65201
      • Recruiting
      • University of Missouri Health Care
  • New Jersey
    • Edison, New Jersey, United States, 08818
      • Completed
      • JFK Medical Center- The Neuroscience Institute
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Northeast Regional Epilepsy Group
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Saint Peter's University Hospital
  • New York
    • Brooklyn, New York, United States, 11215
      • Completed
      • New York Presbyterian Hospital
    • Buffalo, New York, United States, 14203
      • Completed
      • UBMD Neurology
    • Woodmere, New York, United States, 11598
      • Completed
      • Five Towns Neuroscience Research
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Children's Health Center
  • Ohio
    • Columbus, Ohio, United States, 43214
      • Completed
      • Ohio Health Research and Innovation Institute
    • Toledo, Ohio, United States, 43606
      • Recruiting
      • University of Toledo
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Completed
      • Thomas Jefferson University
    • Philadelphia, Pennsylvania, United States, 19104
      • Completed
      • Hospital of the University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Completed
      • Temple University Lewis Katz School of Medicine
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Recruiting
      • LeBonheur Children's Medical Center
    • Nashville, Tennessee, United States, 37232
      • Completed
      • Vanderbilt University Medical Center
  • Texas
    • Austin, Texas, United States, 78757
      • Recruiting
      • Child Neurology Consultants of Austin
    • El Paso, Texas, United States, 79912
      • Recruiting
      • ANRC Research
    • Houston, Texas, United States, 77030
      • Completed
      • Baylor College of Medicine
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • Recruiting
      • University of Utah / Primary Children's Hospital
  • Virginia
    • Roanoke, Virginia, United States, 24016
      • Completed
      • Carilion Clinic
  • Washington
    • Renton, Washington, United States, 98057
      • Completed
      • Valley Medical Center
    • Spokane, Washington, United States, 99204
      • Completed
      • Multicare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; Matching Placebo; Other Names: PBO
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. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.	Drug: Cenobamate; 12.5 mg tablet, 25 mg tablet, 50 mg tablet, 100 mg tablets, 150 mg tablets, 200 mg tablets. Adolescents will follow the same every two week regimen and receive cenobamate as an oral suspension based on weight.; Other Names: YKP3089

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Seizure Diary	Daily seizure diary that contains type and frequency of seizures	28 Days

Collaborators and Investigators

• Sponsor: SK Life Science, Inc.
• Investigators: Study Director: Sunita Misra, MD, SK Life Science, Inc.

Publications and helpful links

General Publications

• Rosenfeld WE, Ferrari L, Kamin M. Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study. Epilepsy Res. 2022 Jul;183:106940. doi: 10.1016/j.eplepsyres.2022.106940. Epub 2022 May 5.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2018
• Primary Completion (Estimated): June 19, 2024
• Study Completion (Estimated): July 19, 2024

Study Registration Dates

• First Submitted: September 18, 2018
• First Submitted That Met QC Criteria: September 18, 2018
• First Posted (Actual): September 20, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Primary Generalized Tonic-Clonic Seizures; Idiopathic Generalized Epilepsy; PGTC; Generalized Tonic-Clonic Seizures
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Epilepsy; Seizures; Epilepsy, Generalized; Anticonvulsants; Cenobamate
• Other Study ID Numbers: YKP3089C025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No