An Open-label Adaptive Study for the Assessment of Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Doses of Radiprodil in Subjects With Drug-resistant Infantile Spasms
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
研究概览
简要总结
The purpose of the study is to evaluate the safety and tolerability, the pharmacokinetics and the efficacy of radiprodil in abolishing clinical spasms in subjects with drug-resistant infantile spasms
详细描述
The study is divided into 3 parts:
Part A - exploratory, Part B - confirmatory, Part C - open label extension
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Months 至 14 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A and B:
- •Subject is male or female between 2 and 14 months of age
- •The diagnosis of infantile spasms (IS)
- •Subject has drug-resistant IS
- •Subject participated in EP0078 Part A and received 2 radiprodil treatment cycles
- •Subject experienced a relapse of spasms during the down taper or within 5 half-lives (3 days) discontinuation of radiprodil treatment in Cycle 2 of Part A
- •Electroencephalogram (EEG) on baseline Part C is compatible with the diagnosis of infantile spasms
排除标准
- •Part A and B:
- •More than 6 months have passed since the diagnosis of Infantile Spasms (IS)
- •Current treatment with cannabinoids
- •Subject has hematocrit greater than 60
- •Subject has any medical condition that, in the opinion of the Investigator, could jeopardize or would compromise the subject's ability to participate in this study
- •Subject has a history or current condition predisposing to respiratory dysfunction
- •Current treatment with felbamate
- •Current treatment with perampanel
- •Ketogenic diet
- •Clinically significant lab abnormalities
- •Clinically significant abnormality on ECG that, in the opinion of the Investigator, increases the safety risks of participating in the study
- •Subject has a lethal or potentially lethal condition other than IS, with a significant risk of death before 18 months of age such as non-ketotic hyperglycinemia
- •Body weight is below 4 kg
- •Known history of severe anaphylactic reaction secondary to medication intake or serious blood dyscrasias
- •Subject experienced any acute tolerability issues in either treatment cycle in Part A which the investigator and the sponsor medical monitor consider a risk for further participation
- •Subject met any withdrawal criteria in Part A
- •Subject has experienced any adverse effects or developed any new medical conditions since enrollment in Part A which the investigator considers could significantly increase the safety risks of participating in Part C
研究组 & 干预措施
Radiprodil
Each subject will enter an individualized dose titration schedule.
干预措施: Radiprodil (Drug)
结局指标
主要结局
Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil
时间窗: Day 14, counting from the first day of radiprodil at maintenance dose
Clinical response is defined as no spasms on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part A.
Estimates of exposure generated from a population-Pharmacokinetic modelling
时间窗: Samples will be taken at baseline (time during Day -14 to -1 prior to dosing) and 3, 4, 5 & 12hr after the 1st dose on Day 1 of radiprodil low, mid & high dose. Blood samples will be taken at same timepoints after 1st dose on Day 2 of radiprodil low dose
This is a primary variable for Part A.
Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil
时间窗: Day 14, counting from the first day of radiprodil at maintenance dose
Electro-clinical response is defined as no spasms and resolution of hypsarrythmia on Day 14 of treatment with the maintenance dose of radiprodil. This is the primary efficacy variable for Part B.
Incidence of Adverse Events (AEs) during the study
时间窗: From Baseline (Day -1) to the end of the Post-treatment Period (28 days post last dosing)
An AE is any untoward medical occurrence in a subject or trial subject that is administered a drug or biologic (medicinal product) or that is using a medical device. The event does not necessarily have a causal relationship with that treatment or usage. This is a primary variable for all parts.
次要结局
- Percentage of subjects with electro-clinical response on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from the first day of radiprodil at maintenance dose)
- Percentage of subjects with clinical response on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Estimates of exposure generated from a population-Pharmacokinetic modelling(Pharmacokinetic samples will be collected on Day 1 of radiprodil low dose, mid dose and high dose. Additionally, blood samples will be taken after 1st dose on Day 2 of radiprodil low dose.)
- Time to cessation of spasms(During the first 14 days of treatment with radiprodil)
- Percentage of responders with clinical relapse(12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Time to clinical relapse from the day of spasm cessation(From day of spasms cessation up to 42 months of age)
- Percentage of electro-clinical responders with electro-clinical relapse(12 months, counting from Day 14 of treatment with the maintenance dose of radiprodil)
- Time to electro-clinical relapse from the day of spasm cessation(From day of spasms cessation up to 42 months of age)
- Percentage of subjects with extended clinical response(28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil)
- Percentage of subjects with extended electro-clinical response(28 days, counting from Day 14 (inclusive) of treatment with the maintenance dose of radiprodil)
- Percentage of subjects with extended clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil(28 days, counting from Day 14 (inclusive) of maintenance dose)
- Number of treatment cycles per subject(During Part C (Day -1 to Day 28 of the Maintenance Period))
- Percentage of subjects with electro-clinical response to each additional treatment cycle on Day 14 of treatment with the maintenance dose of radiprodil(Day 14, counting from the first day of maintenance dose)
- Time to clinical relapse from the first day of no witnessed spasms for each treatment cycle(From day of no witnessed spasms up to 42 months of age)