A Multicenter, 2-Cohort Trial to First Assess the Pharmacokinetic and Safety Profile of a Single Dose of ZX008 (Fenfluramine Hydrochloride) Oral Solution When Added to Standard of Care (Cohort 1), Followed by a Randomized, Double-blind, Placebo-controlled Parallel Group Evaluation of the Efficacy, Safety, and Tolerability of ZX008 as Adjunctive Antiepileptic Therapy to Stiripentol Treatment in Children and Young Adults With Dravet Syndrome (Cohort 2)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 87
- 试验地点
- 28
- 主要终点
- Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period
研究概览
简要总结
The primary purpose of this study is to evaluate the safety, tolerability, and efficacy of ZX008 (fenfluramine hydrochloride) when added to adjunctive antiepileptic stiripentol treatment in children and young adults with Dravet syndrome.
详细描述
This is a multicenter, 2-cohort trial to first assess the pharmacokinetic and safety profile of a single dose of ZX008 (fenfluramine hydrochloride) oral solution when added to a standard Dravet syndrome treatment regimen containing valproate (VPA) and clobazam (CLB), with or without stiripentol (STP) (Cohort 1), followed by a randomized, double-blind, placebo-controlled parallel group evaluation of the efficacy, safety, and tolerability of ZX008 as adjunctive therapy for seizures in children and young adults with Dravet syndrome (Cohort 2).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be male or non-pregnant, non-lactating female, aged 2 to 18 years (inclusive).
- •Subject must have documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
- •Subject must be receiving a therapeutically relevant and stable dose of stiripentol (STP) plus clobazam (CLB) and/or valproate (VPA), and for at least 4 weeks prior to screening and be expected to remain stable throughout the study (Cohort 2 only).
- •Subject must be receiving a stable dose of CLB and VPA, administered twice daily (BID), to be eligible for Dose Regimen 1 and 2, or subject must be receiving a stable dose of CLB, VPA, and STP, administered BID, to be eligible for Dose Regimen 3 (Cohort 1 only).
排除标准
- •Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
- •Subject has pulmonary arterial hypertension.
- •Subject has a current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction, or stroke.
- •Subject has a current or recent history of anorexia nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
- •Subject has a current or past history of glaucoma.
- •Subject is receiving concomitant therapy with: centrally acting anorectic agents; monoamine-oxidase inhibitors; any centrally acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; triptans, atomoxetine, or other centrally acting noradrenergic agonists; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
- •Subject is currently taking carbamazepine ,oxcarbazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy.
- •Subject has a positive result on urine tetrahydrocannabinol (THC) panel or whole blood cannabidiol (CBD) at the Screening Visit.
- •Subject has a clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
研究组 & 干预措施
Cohort 2: ZX008 0.5 mg/kg/day
ZX008 0.5 mg/kg/day (maximum 20 mg/day) dose supplied as an oral solution administered twice a day (BID) in equally divided doses with food.
干预措施: ZX008 (Fenfluramine Hydrochloride) (Drug)
Cohort 2: Matching Placebo
Matching placebo administered twice a day (BID) in equally divided doses with food.
干预措施: Matching Placebo (Drug)
结局指标
主要结局
Change in Convulsive Seizure Frequency (CSF) From the Baseline Period (Baseline) to the Combined Titration + Maintenance (T+M) Period
时间窗: 15 weeks (combined Titration + Maintenance Period)
Monthly (28 day) convulsive seizure frequency (CSF) was based on electronic diary data obtained for each participant. Convulsive seizures included hemiclonic, focal with clear observable motor signs, generalized tonic clonic, secondarily generalized tonic clonic, tonic, clonic, and drop seizures (tonic/atonic). The number of convulsive seizures reported during the entire time interval was divided by the number of nonmissing diary days and the result was then multiplied by 28 to get a 28-day CSF.
次要结局
- Percentage of Participants Who Achieved ≥ a 50% Reduction in Convulsive Seizure Frequency From Baseline to the Combined Titration + Maintenance Period(15 weeks (combined Titration + Maintenance Period))
- Longest Convulsive Seizure-Free Interval (Days)(15 weeks (combined Titration + Maintenance Period))