NCT05219617招募中3 期
A Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Carisbamate (YKP509) as Adjunctive Treatment for Seizures Associated With Lennox-Gastaut Syndrome in Children and Adults, With Optional Open-Label Extension
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 252
- 试验地点
- 71
- 主要终点
- 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.
研究概览
简要总结
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).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
盲法说明
Double-blind study
入排标准
- 年龄范围
- 4 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Carisbamate 200 mg BID arm
Experimental
Age: 4 to <12y* Titration: 2 mg/kg BID Maintenance: 4 mg/kg BID
Age: ≥12 y Titration: 100 mg BID Maintenance: 200 mg BID
干预措施: Carisbamate (Drug)
Carisbamate 300 mg BID arm
Experimental
Age: 4 to <12y* Titration: 2.75 mg/kg BID Maintenance: 5.5 mg/kg BID
Age: ≥12 y Titration: 150 mg BID Maintenance: 300 mg BID
干预措施: Carisbamate (Drug)
Placebo matched to 200 mg BID arm
Placebo Comparator
Age: 4 to <12y* Titration: Volume equivalent to 2 mg/kg BID Maintenance: Volume equivalent to 4 mg/kg BID
Age: ≥12 y Titration: Volume equivalent to 100 mg BID Maintenance: Volume equivalent to 200 mg BID
干预措施: Carisbamate (Drug)
Placebo matched to 300 mg BID arm
Placebo Comparator
Age: 4 to <12y* Titration: Volume equivalent to 2.75 mg/kg BID Maintenance: Volume equivalent to 5.5 mg/kg BID
Age: ≥12 y Titration: Volume equivalent to 150 mg BID Maintenance: Volume equivalent to 300 mg BID
干预措施: Carisbamate (Drug)
结局指标
主要结局
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.
时间窗: 3 years
Efficacy of Carisbamate YKP509
次要结局
- Percentage change from baseline in the frequency of all types of seizures (total seizures) during the double-blind treatment period.(3 years)
- 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.(3 years)
- Subject/Caregiver Global Impression of Change (S/CGIC) in overall condition score at the last visit.(3 years)
研究者
研究点 (71)
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