Resumen

El objetivo primario es evaluar la eficacia de carisbamate (YKP509) como tratamiento coadyuvante para reducir el número de crisis de caída (tónicas, atónicas y tonicoclónicas) en comparación con placebo en sujetos pediátricos y adultos (de 4 a 55 años) con diagnóstico de Síndrome de Lennox-Gastaut (SLG).

Descripción detallada

Los objetivos secundarios son: * Evaluar la eficacia de carisbamate (YKP509) como tratamiento coadyuvante para reducir el número total de crisis en comparación con placebo en sujetos pediátricos y adultos con diagnóstico de Síndrome de Lennox-Gastaut (SLG). * Evaluar la seguridad y tolerabilidad de carisbamate en la población con SLG. * Evaluar la farmacocinética en estado estacionario de carisbamate en sujetos con Síndrome de Lennox-Gastaut.

Elegibilidad

Edad mínima: 4 YearsEdad máxima: 55 YearsSexo: ALL

Criterios de inclusión

Subject must have a documented history of Lennox-Gastaut syndrome by:
Evidence of more than one type of seizure, of which at least one should be an atonic or tonic seizure
History of an electroencephalogram (EEG) reporting diagnostic criteria for LGS (abnormal background activity accompanied by slow, spike and wave pattern \<3.0 Hz)
History of developmental delay
Male or female subjects
Subjects must be age 4-55 years at the time of consent/assent
Must have been \<11 years old at the onset of LGS
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).
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
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.
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.
Parents or caregivers must be able to keep accurate seizure diaries
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.
Subject and/or caregiver(s)/legal representative must be willing and able to give informed assent/consent for participation in the study
Subject and their caregiver must be willing and able (in the investigator's opinion) to comply with all study requirements
History of COVID-19 vaccination is permitted

Criterios de exclusión

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
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
Subjects who were on adrenocorticotropic hormone (ACTH) therapy in the 6 months prior to baseline
Subject on dietary therapy for less than 4 weeks prior to screening visit (Visit 1) or suffers from frequent stooling
Current use of felbamate with less than 18 months of continuous exposure
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.
Subject who had a history of hypoxia which needed emergency resuscitation within 12 months prior to baseline
Status epilepticus within 12 weeks prior to Visit 1
Any clinically significant illness (including COVID-19) in the 4 weeks prior to Visit 1, as evaluated by the Investigator
Subject has clinically significant abnormal laboratory values, in the investigator's opinion, at Visit 1 or time of randomization (Visit 2)
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
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.
Subject is pregnant, may be pregnant, lactating or planning to be pregnant
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
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.
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
Subject with total bilirubin \[TBL\] \>2 x ULN (except for Gilbert's syndrome).
Active viral hepatitis (B or C) as demonstrated by positive serology at the Screening visit (Visit 1)
History of positive antibody/antigen test for human immunodeficiency virus (HIV)
If taking Epidiolex, subject may not use other approved cannabidiol or over the counter cannabidiol products
Scheduled for epilepsy-related surgery, VNS insertion, or any other stimulators/surgery during the projected course of the study
Subject who has taken or used any investigational drug or device in the 4 weeks prior to the screening visit (Visit 1)
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
Evidence of cardiac disease, including unstable angina, myocardial infarction, within the past 2 years, uncontrolled heart failure, major arrhythmias, congenital short QT syndrome
Subject with a short QTc interval (\<340 msec) or long QTc interval (\>460 msec) as confirmed by a repeated electrocardiogram (ECG)
Benzodiazepine rescue administered on average more than once a week in the month before Visit 1
Previous exposure to carisbamate or sensitivity/allergy to components of the oral suspension.

Intervenciones

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 \[or a total of 600 mg per day\]).

Un Estudio Aleatorizado, Doble Ciego, Controlado con Placebo para Investigar la Eficacia y Seguridad de Carisbamate (YKP509) como Tratamiento Coadyuvante para las Crisis Asociadas con el Síndrome de Lennox-Gastaut en Niños y Adultos, con Extensión Abierta Opcional

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Carisbamate

Ubicaciones

Hospital de Ninos de La Santisma Trinidad

Resolution Psychopharmacology Research Institute

Patrocinadores

Contactos

Barbara Remes