An Open-Label Extension Trial to Assess the Long-Term Safety of ZX008 (Fenfluramine Hydrochloride HCl) Oral Solution as an Adjunctive Therapy in Children and Young Adults With Dravet Syndrome
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 375
- 试验地点
- 67
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period
研究概览
简要总结
This is an international, multicenter, open-label, long-term safety study of ZX008 in subjects with Dravet syndrome.
详细描述
This is an international, multicenter, open-label, long-term safety study of ZX008 in pediatric and young adult subjects with Dravet syndrome who participated in one of the core studies (ZX008-1501 and ZX008-1502) and are candidates for continuous treatment for an extended period of time. This trial will consist of a 36-month Open-Label Extension (OLE) Treatment Period and a 2-week Post-Dosing Period.
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 Years 至 35 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-lactating female, age 2 to 18 years, inclusive as of the day of the core study Screening Visit.
- •Satisfactory completion of the core study in the opinion of the investigator and the sponsor.
- •Subjects who are >18 to ≤35 years of age at the time of screening and did not participate in one of the core studies may be eligible for participation.
- •A documented medical history to support a clinical diagnosis of Dravet syndrome, where convulsive seizures are not completely controlled by current antiepileptic drugs.
- •Parent/caregiver is willing and able to be compliant with diary completion, visit schedule and study drug accountability.
- •Subject's parent/caregiver has been compliant with diary completion during the core study, in the opinion of the investigator (eg, at least 90% compliant).
排除标准
- •Current or past history of cardiovascular or cerebrovascular disease, myocardial infarction or stroke.
- •Current cardiac valvulopathy or pulmonary hypertension that is clinically significant and warrants discontinuation of study medication.
- •Current or past history of glaucoma.
- •Moderate or severe hepatic impairment.
- •Receiving concomitant therapy with: centrally-acting anorectic agents; monoamineoxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; atomoxetine, or other centrally-acting noradrenergic agonist; cyproheptadine, and/or cytochrome P450 (CYP) 2D6/3A4/2B6 inhibitors/substrates.
- •Currently taking carbamazepine, oxcarbamazepine, eslicarbazepine, phenobarbital, or phenytoin, or has taken any of these within the past 30 days, as maintenance therapy.
- •A clinically significant condition, or has had clinically relevant symptoms or a clinically significant illness at Visit 1, 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
ZX008
ZX008 is supplied as an oral solution in a concentration of 2.5 mg/mL. Subjects will be titrated to an effective dose beginning with 0.2 mg/kg/day (maximum: 30 mg/day).
干预措施: ZX008 (Fenfluramine Hydrochloride) (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) During the Open-label Extension (OLE) Treatment Period
时间窗: From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42)
Treatment-emergent adverse events (TEAE) were defined as any AEs that based on start date information occurs after the first intake of study treatment.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Leading to Withdrawal From Investigational Medicinal Product (IMP) During the OLE Treatment Period
时间窗: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
A TEAE was defined as any AE that based on start date information occurs after the first intake of study treatment. Percentage of participants with TEAEs leading to withdrawal from IMP during OLE Treatment Period were reported.
Percentage of Participants With Serious Treatment-emergent Adverse Events (TEAEs) During the OLE Treatment Period
时间窗: From Day 1 to End of OLE Treatment Period - EOS Visit (Month 42)
Serious Adverse event (SAE) was defined as any untoward medical occurrence that at any dose: • results in death, • is life-threatening threatening, • results in initial inpatient hospitalization or prolongation of hospitalization, •results in persistent or significant disability or incapacity, • results in a congenital anomaly/birth defect, • results in any medically significant event that did not meet any of the other 5 SAE criteria, but which was judged by a physician to potentially jeopardize the participant or require medical or surgical intervention to prevent one of the above outcomes listed as an SAE criterion.
次要结局
- Convulsive Seizure Frequency (CSF) Per 28 Days During the OLE Treatment Period (to Month 36)(At Month 1, Month 2, Month 3, Month 4-6, Month 7-9, Month 10-12, Month 13-15, Month 16-18, Month 19-21, Month 22-24, Month 25-27, Month 28-30, Month 31-33, and Month 34-36)
- Percentage of Participants With Changes in Antiepileptic Drug (AED) Medications During First 6 Months of OLE Treatment Period(At Month 1, 2, 3, 4 , 5, and 6 of OLE Treatment Period)
- Convulsive Seizure Frequency (CSF) by Mean Daily Dose During the Overall OLE Treatment Period(From Day 1 to End of OLE Treatment Period - End of Study (EOS) Visit (Month 42))
- Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Day 1 to End of Study (EOS) Visit (Month 42) in the OLE Treatment Period(From Day 1 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core))
- Change From Baseline (Core) in Convulsive Seizure Frequency Per 28 Days From Month 2 to EOS (Month 42) in the OLE Treatment Period(From Month 2 to End of OLE Treatment Period (EOS Visit - up to Month 42), compared to Baseline (Core))