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

NCT03678753 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: YKP3089C025
• Study Type: interventional
• Target: 169
• Locations: 12 countries
• Sites: 116

Brief Summary

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.

Conditions

Primary Generalized Epilepsy

Keywords

Primary Generalized Tonic-Clonic Seizures; PGTC; Idiopathic Generalized Epilepsy; Generalized Tonic-Clonic Seizures

Outcome Measures

Primary Outcomes (1)

• Seizure Diary

  Daily seizure diary that contains type and frequency of seizures

  28 Days

Study Arms (2)

Cenobamate

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

Cenobamate DRUG

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.

Also known as: YKP3089

Cenobamate

Placebo DRUG

Matching Placebo

Also known as: PBO

Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject is male or female and aged ≥12 years.
• 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.
• Female subjects of childbearing potential are willing to use an acceptable form of birth control
• Subject has a clinical diagnosis of PGTC seizures (with or without other subtypes of generalized seizures) in the setting of idiopathic generalized epilepsy.
• Subject experiences at least 5 PGTC seizures in 12 weeks during the Pre-Randomization Period.
• 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.
• 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.
• 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).
• 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.
• 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.
• 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.

You may not qualify if:

• Female subjects who are pregnant (or planning to become pregnant during the study), lactating, or breast-feeding.
• Subject has a history o f status epilepticus that required hospitalization within 12 months prior to Visit 1 (Screening/Baseline).
• Subject has PGTC seizure clusters where individual seizures cannot be counted or classified.
• Subject has a history of non-epileptic psychogenic seizures.
• Subject has a concomitant diagnosis of Partial Onset Seizures (POS).
• Subject has a clinical diagnosis of Lennox-Gastaut syndrome.
• 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.
• Subject has participated in previous cenobamate clinical studies.
• 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.
• 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).
• Subject has received an investigational drug or device within 30 days prior to Visit 1 (Screening/Baseline).
• Subject has a history of drug or alcohol dependency or abuse within 2 years prior to Visit 1 (Screening/Baseline).
• 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).
• 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.

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (116)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Center for Neurosciences

Tucson, Arizona, 85718, United States

Location

Neuro Pain Medical Center

Fresno, California, 93710, United States

Location

Colorado Springs Neurological Associates

Colorado Springs, Colorado, 80907, United States

Location

Children's Hospital of Colorado

Grand Junction, Colorado, 80045, United States

Location

Brainstorm Research

Miami, Florida, 33176, United States

Location

Florida Hospital Medical Group

Orlando, Florida, 32803, United States

Location

University of South Florida

Tampa, Florida, 33606, United States

Location

Clinical Integrative Research Center of Atlanta, CIRCA

Atlanta, Georgia, 30328, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30329, United States

Location

Hawaii Pacific Neuroscience

Honolulu, Hawaii, 96814, United States

Location

Consultants in Epilepsy and Neurology

Boise, Idaho, 83702, United States

Location

Rush University

Chicago, Illinois, 60612, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

PMG Research of McFarland Clinic

Ames, Iowa, 50010, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Maine Medical Center

Scarborough, Maine, 04074, United States

Location

Mid-Atlantic Epilepsy and Sleep Center

Bethesda, Maryland, 20817, United States

Location

Michigan State University

East Lansing, Michigan, 48824, United States

Location

Minneapolis Clinic of Neurology Golden Valley

Golden Valley, Minnesota, 55422, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

University of Missouri Health Care

Columbia, Missouri, 65201, United States

Location

JFK Medical Center- The Neuroscience Institute

Edison, New Jersey, 08818, United States

Location

Northeast Regional Epilepsy Group

Hackensack, New Jersey, 07601, United States

Location

Saint Peter's University Hospital

New Brunswick, New Jersey, 08901, United States

Location

New York Presbyterian Hospital

Brooklyn, New York, 11215, United States

Location

UBMD Neurology

Buffalo, New York, 14203, United States

Location

Five Towns Neuroscience Research

Woodmere, New York, 11598, United States

Location

Duke University Children's Health Center

Durham, North Carolina, 27710, United States

Location

Ohio Health Research and Innovation Institute

Columbus, Ohio, 43214, United States

Location

University of Toledo

Toledo, Ohio, 43606, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Temple University Lewis Katz School of Medicine

Philadelphia, Pennsylvania, 19140, United States

Location

LeBonheur Children's Medical Center

Memphis, Tennessee, 38105, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Child Neurology Consultants of Austin

Austin, Texas, 78757, United States

Location

ANRC Research

El Paso, Texas, 79912, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah / Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Carilion Clinic

Roanoke, Virginia, 24016, United States

Location

Valley Medical Center

Renton, Washington, 98057, United States

Location

MultiCare Institute for Research and Innovation

Spokane, Washington, 99204, United States

Location

Austin Health

Heidelberg, 3084, Australia

Location

Children's Health Queensland Hospital

South Brisbane, 4101, Australia

Location

MHAT Sv. Ivan Rilski Gorna Oryahovitsa EOOD

Gorna Oryahovitsa, Veliko Tarnovo, 5100, Bulgaria

Location

Multiprofile Hospital for Active Treatment Puls AD

Blagoevgrad, 2700, Bulgaria

Location

UMHAT Kanev AD

Rousse, 7002, Bulgaria

Location

MHAT Lyulin EAD

Sofia, 1336, Bulgaria

Location

Acibadem City Clinic MHAT Tokuda EAD

Sofia, 1407, Bulgaria

Location

Diagnostic Consultative Center Neoclinic EAD

Sofia, 1408, Bulgaria

Location

Diagnostic Consultative Center Equita EOOD

Varna, 9000, Bulgaria

Location

Medical Center Medica Plus OOD

Veliko Tarnovo, 5000, Bulgaria

Location

Fakultní nemocnice v Motole

Prague, Prague, 150 06, Czechia

Location

Fakultni nemocnice u sv. Anny v Brne, 1. Neurologicka klinika

Brno, 656 91, Czechia

Location

Nestatni zdravotnicke zarizeni, privatni ordinance neurologie

Hradec Králové, 500 03, Czechia

Location

Cerebrovaskularni poradna, s.r.o.

Ostrava-Poruba, 708 52, Czechia

Location

Cerebovaskularni poradna s.r.o.

Ostrava-Vitkovice, 703 00, Czechia

Location

Forbeli s.r.o., Neurologicka ordinace

Prague, 160 00, Czechia

Location

Vestra Clinics, s.r.o.

Rychnov nad Kněžnou, 516 01, Czechia

Location

Neurologicka ambulance MUDr.Monika Zahumenska

Zlín, 760 01, Czechia

Location

LEPL Tbilisi State Medical University Givi Zhvania Academic Clinic of Pediatry

Tbilisi, 0159, Georgia

Location

Institute of Neurology and Neuropsychology LTD

Tbilisi, 0186, Georgia

Location

Charite - Universitätsmedizin Berlin - Sozialpädiatrisches Zentrum

Berlin, 13353, Germany

Location

Universitätsklinikum Jena

Jena, Germany

Location

Universitätsklinikum Schleswig-Holstein - Campus Kiel

Kiel, 24105, Germany

Location

Sächsisches Epilepsiezentrum Kleinwachau gGmbH

Radeberg, 01454, Germany

Location

Semmelweis Egyetem

Budapest, 1083, Hungary

Location

Debreceni Egyetem Klinikai Központ, Gyermekgyógyászati Intézet Nagyerdei krt. 98

Debrecen, Hungary

Location

Csongrád Megyei Egészségügyi Elláto Központ Ideggyógyászati Osztály

Hódmezővásárhely, 6800, Hungary

Location

Clinical Research Center Spolka z Ograniczona Odpowiedzialnoscia Medic-R sp. k

Poznan, Greater Poland Voivodeship, 60-848, Poland

Location

Centrum Opieki Zdrowotnej Orkan-Med Stec-Michalska S.J.

Ksawerów, Iodzkie, 95-054, Poland

Location

Centrum Leczenia Padaczki i Migreny

Krakow, Lesser Poland Voivodeship, 31-209, Poland

Location

Centrum Medyczne Plejady

Krakow, Lesser Poland Voivodeship, Poland

Location

Wojewódzki Specjalistyczny Szpital Dziecięcy im. sw. Ludwika sw Krakowie

Krakow, Lesser Poland Voivodeship, Poland

Location

NZOZ Poradnia Zdrowia Psychicznego Antonijczuk Boleslaw

Tyniec Mały, Lower Silesian Voivodeship, 55-040, Poland

Location

Centrum Medyczne Oporów

Wroclaw, Lower Silesian Voivodeship, 52-416, Poland

Location

Instytut Medycyny Wsi im. Witolda Chodzki w Lublinie

Lublin, Lublin Voivodeship, 20-090, Poland

Location

Centrum Medyczne Warszawa Pratia s.a

Warsaw, Masovian Voivodeship, 01-868, Poland

Location

Centrum Medyczne Pratia Katowice

Katowice, Silesian Voivodeship, 40-081, Poland

Location

M.A. LEK A.M. Maciejowscy S.C Centrum Terapii SM

Katowice, Silesian Voivodeship, 40-571, Poland

Location

Gornoslaskie Centrum Medyczne - Samodzielny Publiczny Szpital Kliniczny Number 7

Katowice, Silesian Voivodeship, 40-635, Poland

Location

Niepubliczny Zaklad Opieki Zdrowotnej Novo-Med

Katowice, Silesian Voivodeship, 40-650, Poland

Location

Gyncentrum Clinic Sp. z.o.o

Katowice, Silesian Voivodeship, 40-851, Poland

Location

Wojewodzki Szpital Specjalistyczny w Olsztynie

Olsztyn, Warmian-Masurian Voivodeship, 10-561, Poland

Location

Niepubliczny Zakład Opieki Zdrowotnej - Centrum Neurologii Dziecięcej i Leczenia Padaczki

Kielce, Świętokrzyskie Voivodeship, Poland

Location

Konzílium, s.r.o

Dubnica nad Váhom, Trenčín Region, 018 41, Slovakia

Location

MUDr. Beata Dupejova, neurologická ambulncia, s.r.o

Banská Bystrica, 974 04, Slovakia

Location

IN MEDIC s.r.o

Bardejov, 085 01, Slovakia

Location

Narodny Ustav Detskych Chorob

Bratislava, Slovakia

Location

MEDBAJ, s.r.o., Neurologicka ambulancia, Nemocnicna 1944/10

Dolný Kubín, 026 01, Slovakia

Location

NEURES, s.r.o.-Neurologická Ambulancia

Krompachy, 053 42, Slovakia

Location

CHA Bundang Medical Center

Seongnam-si, Gyeonggi-do, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, Gyeonggi-do, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29011, Spain

Location

Hospital Universitario La Fe

Valencia, 46026, Spain

Location

Municipal Non-profit Enterprise City Clinical Hospital No.16 of Dnipro City Council, Department of Neurology

Dnipro, Dnipropetrovsk Oblast, 49069, Ukraine

Location

Communal Enterprise Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov of Dnipropetrovsk Regional Council, Regional Center of Psychosomatic Disorders based on Psychoneurology Department

Dnipro, Dnipro, 49005, Ukraine

Location

Kyiv City Psychoneurological Hospital №2

Kiev, Kyiv Oblast, 02192, Ukraine

Location

Municipal Non-Profit Enterprise Odesa Regional Clinical Hospital of Odesa Regional Council, Department of Cerebro-Vascular Diseases with Neurosurgery

Odesa, Odesa Oblast, 65025, Ukraine

Location

Municipal Non-profit Enterprise Regional Clinical Center of Neurosurgery and Neurology of Zakarpattia Regional Council, Department of Neurosurgery #2

Uzhhorod, Zakarpattia Oblast, 88018, Ukraine

Location

Municipal Non-Profit Enterprise Zaporizhzhia Regional Clinical Hospital Of Zaporizhzhia Regional Council

Zaporizhzhya, Zaporizhzhya, 69600, Ukraine

Location

Communal Enterprise Regional Medical Center of Family Health of the Dnipropetrovsk Regional Council

Dnipro, 49000, Ukraine

Location

Communal Non-commercial Enterprise City Children's Clinical Hospital 6 of Dnipro City Council

Dnipro, 49009, Ukraine

Location

Communal Enterprise Dnipropetrovsk Regional Clinical Hospital n.a. I.I. Mechnykov of Dnipropetrovsk Regional Council

Dnipropetrovsk, 49005, Ukraine

Location

Municipal Non-profit Enterprise Prykarpattia Regional Clinical Center for Mental Health of Ivano-Frankivsk Regional Council

Ivano-Frankivsk, 76011, Ukraine

Location

Communal Non-Commercial Enterprise of Kharkiv Regional Council Regional Clinical Psychiatric Hospital #3

Kharkiv, 61068, Ukraine

Location

Communal Non-Profit Enterprise of Lviv Regional Council Lviv Regional Clinical Hospital, Neurological Department, Antiepileptic Center

Lviv, 79010, Ukraine

Location

Communal Non-Profit Enterprise Odesa Regional Medical Centre of Mental Health Odesa Regional Council, Department #2

Odesa, 67513, Ukraine

Location

Odessa Regional Psychiatric Hospital No. 2,

Odesa, 67513, Ukraine

Location

Communal Enterprise Poltava Regional Clinical Psychiatric Hospital named after O.F. Maltsev of Poltava Regional Council

Poltava, 36000, Ukraine

Location

Municipal Non-Profit Enterprise Ternopil Regional Clinical Psychoneurological Hospital of Ternopil Regional Council, Department of Neurology #2

Ternopil, 46020, Ukraine

Location

Municipal Non-profit Enterprise Vinnytsia Regional Clinical Psychoneurological Hospital named after Acad. O.I. Yushchenko of Vinnytsia Regional Council, Department of Neurology #3

Vinnytsia, 21005, Ukraine

Location

Related Publications (2)

• Brigo F, Lattanzi S. Cenobamate add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. 2024 Aug 1;8(8):CD014941. doi: 10.1002/14651858.CD014941.pub2.

  PMID: 39087564 DERIVED

• 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.

  PMID: 35605481 DERIVED

MeSH Terms

Conditions

Epilepsy, Idiopathic Generalized; Seizures

Interventions

Cenobamate

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Sunita Misra, MD

  SK Life Science, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2018
• First Posted: September 20, 2018
• Study Start: September 21, 2018
• Primary Completion: May 26, 2025
• Study Completion: May 26, 2025
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (16); CZ (8); UA (17); AU (2); DE (4); HU (3); US (43); KR (4); SL (6); ES (3); BU (8); GE (2)