A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial With an Open-Label Extension Phase ofPerampanel as Adjunctive Treatment in Subjects at Least 2 years of Age With Inadequately Controlled SeizuresAssociated With Lennox-Gastaut Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 142
- 试验地点
- 10
- 主要终点
- To demonstrate that perampanel given as adjunctive antiepileptic treatment is superior to placebo in reducing the incidence of drop seizures in subjects with inadequately controlled seizures associated with LGS
研究概览
简要总结
This will be amulticenter, double-blind, randomized, placebo-controlled, parallel-group studyof perampanel as adjunctive therapy in subjects with inadequately controlledseizures associated with LGS. The study will consist of 3 phases:Prerandomization (4- to 8-week Screening/Baseline Period), Randomization(6-week Titration, 12-week Maintenance, and 4-week Follow-up, only for subjectsnot entering into Extension A), and Extension (Extension A and Extension B). Extension A will consist of 6-week blindedConversion Period, 46-week Maintenance Period, and 4-week Follow-up (for thosesubjects not entering into Extension B). Extension B is planned to be implemented in Japan and in countries wherean Extended Access Program cannot be implemented or has not yet beenimplemented.
Following theScreening/Baseline Period, eligible subjects will be randomized to receiveperampanel or placebo in a 1:1 ratio. During the Randomization Phase, perampanel (or matching placebo) will beadministered once daily at a starting dose of 2 mg and up-titrations to amaximum target dose of 8 mg according to individual tolerability andefficacy. During Extension A, subjectsin the perampanel group during the Randomization Phase will continue with perampaneltreatment at the same dose received at the end of the Randomization Phase. Subjects in the placebo group during theRandomization Phase will begin treatment with perampanel in a blinded mannerstarting at 2 mg/day and then up-titrated to a target dose of 8 mg/day. After the double-blind Conversion Period, furtherup-titrations up to 12 mg/day (except in Japan, where the maximum allowed doseremains at 8 mg/day) is allowed at the discretion of the investigator.Addition, deletion, and dose changes to the concomitant AEDs are allowed duringExtension Maintenance Period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Double Blind Double Dummy
入排标准
- 年龄范围
- 2.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Subjects must have diagnosis of Lennox-Gastaut Syndrome (LGS) 2.At least 2 years old at the time of consent/assent 3.Age of LGS onset must be <11 years old 4.Must have an average of at least 2 drop seizures per week in the 4-week Baseline Period 5.Must be taking 1 to 4 concomitant anti-epileptic drugs (AEDs) at a stable dose for at least 30 days before Visit 1.
排除标准
- •1.Presence of progressive neurological disease 2.Presence of drop seizure clusters where individual seizures cannot be reliably counted 3.Prior treatment with perampanel with discontinuation due to safety issues related to perampanel or recent treatment with perampanel within 30 days before Screening 4.Scheduled for epilepsy-related surgery or other surgery during the study 5.Status epilepticus within 12 weeks before Screening 6.Current use of felbamate of less than 1 year, or with dose changes within 60 days before Screening, or history of hematological/hepatic function test abnormalities or other indication of hepatic/bone marrow dysfunction while receiving felbamate.
- •7.Current or recent use of vigabatrin within 5 months of Screening, or history of vigabatrin-associated clinically significant abnormality in an automated visual perimetry test 8.Intermittent use of benzodiazepine of more than 4 single administrations in the month before Screening 9.Psychotic disorders or unstable recurrent affective disorders evident by use of antipsychotics or prior suicide attempts within approximately the last 2 years 10.Use of AEDs not recommended by Epilepsy Treatment Guidelines for use in LGS 11.Any suicidal ideation with intent with or without a plan within 6 months before Randomization Visit.
结局指标
主要结局
To demonstrate that perampanel given as adjunctive antiepileptic treatment is superior to placebo in reducing the incidence of drop seizures in subjects with inadequately controlled seizures associated with LGS
时间窗: Median percent change in drop seizure frequency per 28 days
次要结局
- To demonstrate that perampanel adjunctive treatment is superior to placebo in the 50%, 75%, and 100% responder rates for drop seizures in subjects with inadequately controlled seizures associated with LGS(50% responder rate for drop seizures)
- To evaluate the 50%, 75%, and 100% responder rates in non-drop seizure frequency(50%, 75%, and 100% responder rates for non-drop seizures)
- To demonstrate that perampanel adjunctive treatment is superior to placebo in the 50%, 75%, and 100% responder rates for total seizures in subjects with inadequately controlled seizures associated with LGS(50% responder rate for total seizures)
- To demonstrate that perampanel adjunctive treatment is superior to placebo in reducing the incidence of all seizures in subjects with inadequately controlled seizures associated with LGS(Median percent change in total seizure frequency per 28 days)
- To demonstrate that perampanel adjunctive treatment is superior to placebo in reducing the incidence of non-drop seizures in subjects with inadequately controlled seizures associated with LGS(Median percent change in non-drop seizure frequency per 28 days)
- To evaluate physicians’ global evaluation of subjects’ overall changes in symptomsPhysicians’ global evaluation of the subject’s overall changes in symptoms(Physicians’ global evaluation of the subject’s overall changes in symptoms)
- To evaluate the safety of perampanel relative to placebo as adjunctive therapy in subjects with inadequately controlled seizures associated with LGS(Incidence of AEs and SAEs, changes in clinical laboratory values, and vital signs)
- To evaluate the pharmacokinetics (PK) and the pharmacokinetic/pharmacodynamic (PK/PD) relationships of perampanel as adjunctive therapy in subjects with inadequately controlled seizures associated with LGS(Model-derived average perampanel concentrations at steady state (Cav,ss))