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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05219617
Other study ID # YKP509C003
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date April 28, 2022
Est. completion date June 2026

Study information

Verified date May 2024
Source SK Life Science, Inc.
Contact Barbara Remes
Phone 201-421-3810
Email bremes@sklsi.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The primary objective is to evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the number of drop seizures (tonic, atonic, and tonic-clonic) compared with placebo in pediatric and adult subjects (age 4-55 years) diagnosed with Lennox Gastaut Syndrome (LGS).


Description:

The secondary objectives are: - To evaluate the efficacy of carisbamate (YKP509) as adjunctive treatment in reducing the total number of seizures compared with placebo in pediatric and adult subjects diagnosed with Lennox Gastaut Syndrome (LGS) - Evaluate the safety, tolerability of carisbamate in the LGS population - Evaluate steady-state pharmacokinetics of carisbamate in subjects with Lennox Gastaut.


Recruitment information / eligibility

Status Recruiting
Enrollment 252
Est. completion date June 2026
Est. primary completion date June 2025
Accepts healthy volunteers No
Gender All
Age group 4 Years to 55 Years
Eligibility Inclusion Criteria: 1. Subject must have a documented history of Lennox-Gastaut syndrome by: 1. Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure 2. History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern <3.0 Hz) 3. History of developmental delay 2. Male or female subjects 3. Subjects must be age 4-55 years at the time of consent/assent 4. Must have been <11 years old at the onset of LGS 5. Subjects must have experienced at least 2 drop seizures with potential to fall (tonic, atonic, tonic-clonic) during the 4-week Baseline period preceding randomization (minimum of 4 drop seizures in the first two weeks and 4 in the last two weeks). Drop seizures are defined as a seizure involving the entire body, trunk, or head that led or could have led to a fall, injury, slumping in a chair, or hitting the subject's head on a surface. All drop seizure types must be countable (either as isolated seizures or as countable isolated seizures in a cluster). 6. Subjects must have been receiving 1 to 4 concomitant anti-seizure medications (ASMs) at a stable dose for at least 4 weeks before Visit 1 7. If not taking Epidiolex, subjects may take other approved cannabidiol or over the counter cannabidiol products. If taking cannabidiol other than Epidiolex, consult Medical Monitor to determine if it counts as a concomitant ASM. 8. Dietary therapy and any CNS stimulator settings must be stable for 4 weeks prior to baseline and maintain stable regimen throughout the study. The dietary therapy and CNS stimulators are not counted as an ASM. 9. Parents or caregivers must be able to keep accurate seizure diaries 10. Subject is either not of childbearing potential, defined as premenarchal, postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), if of childbearing potential, must comply with an acceptable method of birth control during the study, for at least 4 weeks prior to study entry and for 4 weeks following completion of the study, if able. 11. Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study 12. Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements 13. History of COVID-19 vaccination is permitted Exclusion Criteria: 1. Etiology of subject's seizures is a progressive neurologic disease. Subjects with tuberous sclerosis will not be excluded from study participation, unless there is a progressive brain tumor 2. Evidence of clinically significant disease (e.g., cardiac, respiratory, gastrointestinal, renal disease, hepatic disease) that in the opinion of the investigator(s) could affect the subject's safety or study conduct 3. Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline 4. Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling 5. Current use of felbamate with less than 18 months of continuous exposure 6. Concomitant use of vigabatrin: subjects who took vigabatrin in the past must be discontinued for at least 5 months before Visit 1 and must have documentation showing no evidence of a vigabatrin-associated clinically significant abnormality in an automated visual perimetry test, if able. 7. Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline 8. Status epilepticus within 12 weeks prior to Visit 1 9. Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator 10. Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2) 11. Subject has a history of any serious drug-induced hypersensitivity, e.g., toxic epidermal necrolysis, or Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]) or any drug-related rash requiring hospitalization 12. Vagus Nerve Stimulation (VNS), Deep Brain Stimulation (DBS), Responsive Neurostimulator System (RNS) or other neurostimulation for epilepsy device implanted or activated <5 months year prior to enrollment. Stimulation parameters that have been stable for <4 weeks, or Battery life of unit not anticipated to extend for duration of trial. 13. Subject is pregnant, may be pregnant, lactating or planning to be pregnant 14. Any suicidal ideation with intent, with or without a plan within 6 months before Visit 2 (i.e., answering "Yes" to questions 4 or 5 in the Suicidal Ideation section of the age- specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated 15. Any suicidal behavior within 2 years before Visit 2 (i.e., answering YES to any question in the Suicidal behavior section of the age-specific Columbia-Suicide Severity Rating Scale (C-SSRS) in subjects aged 6 and above who are able to be evaluated. 16. Evidence of significant active hepatic disease. Stable elevations of liver enzymes (alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) due to concomitant medication(s) will be allowed if they are <3 x ULN 17. Subject with total bilirubin [TBL] >2 x ULN (except for Gilbert's syndrome). 18. Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1) 19. History of positive antibody/antigen test for human immunodeficiency virus (HIV) 20. If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products 21. Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study 22. Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1) 23. Concomitant use of medications known to be strong inducers of cytochrome P450 (CYP3A) including, but not limited to: phenobarbital, phenytoin, carbamazepine, primidone, rifampin, troglitazone, St. John's Wort, efavirenz, nevirapine, glucocorticoids (other than topical usage), modafinil, pioglitazone, and rifabutin 24. Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome 25. Subject with a short QTc interval (<340 msec) or long QTc interval (>460 msec) as confirmed by a repeated electrocardiogram (ECG) 26. Benzodiazepine rescue administered on average more than once a week in the month before Visit 1 27. Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Carisbamate
Adolescent subjects 12 to 18 years old will receive the same dose as adults. Subjects 4 to < 12 years old in the carisbamate 200 mg BID arm will receive 4 mg/kg BID (not to exceed 200 mg BID [or a total of 400 mg per day]). Subjects 4 to < 12 years old in the carisbamate 300 mg BID arm will receive 5.5 mg/kg BID (not to exceed 300 mg BID [or a total of 600 mg per day]).

Locations

Country Name City State
Argentina Hospital de Ninos de La Santisma Trinidad Córdoba Cordoba
Argentina Resolution Psychopharmacology Research Institute Mendoza
Australia Austin Hosptial Heidelberg
Australia Alfred Health Melbourne
Australia Perth's Children Hospital Nedlands
Australia Queensland Children's Hospital South Brisbane
Colombia Fundacion Hospital Universidad del Norte Barranquilla
Colombia Fundacion Valle del Lili/Clinic - Outpatient Cali
Colombia CliniSalud del Sur S.A.S - Centro de Investigación Envigado
Colombia Hospital Pabloe Tubon Uribe Medellín
Colombia Institutio Neurologico de Colombia Medellín
Germany Universitatsklinikum Erangen Erlangen Bayern
Germany Kleinwachau Sächsisches Epilepsiezentrum Radeberg Sachsen
Greece Iaso Children's Hospital Maroúsi Attiki
Israel Soroka University Medical Centre Be'er Sheva
Israel Hadassah Medical Center Jerusalem
Israel Sheba Medical Center Ramat Gan
Israel Tela Viv Sourlasky Medical Center Tel Aviv Yafo Tel Aviv
Italy Azienda Ospedaliero Universitaria A Meyer - INCIPIT - PIN Calambrone
Italy Istituto G Gaslini Ospedale Pediatrico IRCCS - INCIPIT - PIN Genova Liguria
Italy ASST Fatebenefratelli Sacco - Ospedale dei Bambini Vittore Buzzi Milano Lombardia
Italy ASST Santi Paolo E Carlo - Azienda Universitaria-Polo Universitaria - San Paolo Milano
Italy Fondazione IRCCS Di Rilievo Nazionale Instituto Milano Lombardia
Italy Azienda Ospedaliera Universitaria Integrata Di Verona Verona
Korea, Republic of Kyungpook National University Chilgok Hospital Daegu
Korea, Republic of Samsung Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Mexico Neurociencias Estudios Clinicos S.C. Culiacán
Mexico Hospital Civil Fray Antonio Alcalde Guadalajara Jalisco
Mexico Clinstile, S.A. de C.V. Mexico City
Poland Centrum Medyczne Plejady Kraków
Poland Szpital Kliniczny im.H.Swiecickiego Uniwersytetu Medycznego im.K.Marcinkowskiego w Poznaniu-Dluga1/2 Poznan Wielkopolskie
Portugal Hospital Garcia de Orta Almada Setubal
Portugal Centro Hospitalar de Lisboa Norte, EPE Lisboa
Portugal Centro Hospitalar de Lisboa Ocidental, EPE - Hospital Sao Francisco Xavier Lisboa
Portugal Centro Hospitalar de Sao Joao, EPE Porto
Serbia Childrens University Hospital Belgrade
Serbia University Clinical Center of Serbia - PPDS Belgrade
Serbia University Clinical Center Kragujevac Kragujevac
Serbia University Clinical Center Nis Niš
Serbia Children and Youth Health Care Institute of Vojvodina Novi Sad
Spain Hospital Sant Joan de Deu - PIN Esplugues De Llobregat Barcelona
Spain Hospital Infantil Universitario Niño Jesus - PIN Madrid
Spain Hospital Ruber Internacional (Grupo Quironsalud) Madrid
Taiwan National Taiwan University Hospital Taipei
Taiwan Taipei Veterans General Hospital Taipei
Taiwan Chang Gung Memorial Hospital Taoyuan
United States Austin Epilepsy Care Center - Clinic/Outpatient Facility Austin Texas
United States Johns Hopkins Hospital Baltimore Maryland
United States Mid-Atlantic Epilepsy and Sleep Center Bethesda Maryland
United States Consultants in Epilepsy and Neurology PLLC Boise Idaho
United States Montefiore Bronx New York
United States University of Missouri School of Medicine Columbia Missouri
United States Neurology Consultants of Dallas, PA - Hospital Dallas Texas
United States Duke University Clinical Research at Pickett Road Durham North Carolina
United States Northeast Regional Epilepsy Group Hackensack New Jersey
United States University of Florida Health Science Center Jacksonville Florida
United States Bluegrass Epilepsy Research, LLC Lexington Kentucky
United States St. Peters Hospital New Brunswick New Jersey
United States University Medical Center New Orleans New Orleans Louisiana
United States AdventHealth Orlando Florida
United States Stanford University Hospital Palo Alto California
United States Children's Hospital of Philadelphia Philadelphia Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States Pediatric Epilepsy and Neurology Specialists Tampa Florida
United States University of South Florida Tampa Florida
United States Axcess Medical Research Wellington Florida
United States Virginia Epilepsy and Neurodevelopmental Clinic at WNC Winchester Virginia
United States Wake Forest University - School of Medicine Winston-Salem North Carolina

Sponsors (1)

Lead Sponsor Collaborator
SK Life Science, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Colombia,  Germany,  Greece,  Israel,  Italy,  Korea, Republic of,  Mexico,  Poland,  Portugal,  Serbia,  Spain,  Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Other Percentage change from baseline in the 28-day frequency of: drop seizures (tonic, atonic, tonic-clonic); non-drop seizures (myoclonic seizures, atypical absence); total seizures during the maintenance phase of the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Other Percentage change from baseline in non-drop seizures (myoclonic seizures, atypical absence) frequency per 28 days during the during the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Other The percentage of subjects with at least a 50% reduction from baseline in the total frequency of drop seizures (tonic, atonic, tonic-clonic) during the maintenance phase of the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Other Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Other Proportion of subjects with a 75%, 90% and 100% response rate for drop seizures (tonic, atonic, tonic-clonic), non-drop seizures, and total seizures during the maintenance phase of the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Primary Primary outcome will be the percentage change from baseline in the total frequency (average per 28 days) of countable drop seizures with potential to fall (tonic, atonic, tonic-clonic) seizures during the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Secondary The percentage of subjects with at least a 50% reduction from baseline in the total frequency of drop seizures (tonic, atonic, tonic-clonic) during the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Secondary Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period. Efficacy of Carisbamate YKP509 3 years
Secondary Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit. Efficacy of Carisbamate YKP509- Scoring will be from 1 to 7 with 1 (very much improved) to 7 (very much worse) 3 years
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