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临床试验/NCT03355209
NCT03355209已完成3 期

A Two-Part Study of ZX008 in Children and Adults With Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized, Double-blind, Placebo-controlled Trial of Two Fixed Doses of ZX008 (Fenfluramine Hydrochloride) Oral Solution as Adjunctive Therapy for Seizures in Children and Adults With LGS, Followed by Part 2: An Open-label Extension to Assess Long-Term Safety of ZX008 in Children and Adults With LGS

Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.72 个研究点 分布在 7 个国家目标入组 296 人开始时间: 2017年11月27日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
3 期
状态
已完成
发起方
入组人数
296
试验地点
72
主要终点
Part 2: Percentage of Participants With Serious TEAEs
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

This is a two-part, multicenter, double-blind, parallel-group, placebo controlled study to evaluate the effect of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS).

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)

盲法说明

Part 1: Double-Blind Part 2: Open-Label

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 35 years, inclusive as of the day of the Screening Visit.
  • •Clinical diagnosis of Lennox-Gastaut syndrome, where seizures that result in drops are not completely controlled by current antiepileptic treatments.
  • •Onset of seizures at 11 years of age or younger.
  • •Abnormal cognitive development.
  • •Must be receiving at least 1 concomitant AED and up to 4 concomitant anti-epileptic treatments.

排除标准

  • •Etiology of seizures is a degenerative neurological disease.
  • •History of hemiclonic seizures in the first year of life.
  • •Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
  • •Pulmonary arterial hypertension.
  • •Current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke.
  • •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.
  • •Taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
  • •Currently receiving an investigational product.
  • •Institutionalized in a general nursing home (ie, in a facility that does not specialize in epilepsy care).
  • •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

ZX008 0.2 or 0.8 mg/kg/day

Experimental

Part 1: ZX008 is supplied as an oral solution. Subjects will be randomized to receive 1 of 2 doses of ZX008 0.2 mg/kg/day or 0.8 mg/kg/day.

干预措施: ZX008 0.2 or 0.8 mg/kg/day (Drug)

Matching Placebo

Placebo Comparator

Part 1: Matching ZX008 placebo is supplied as an oral solution.

干预措施: Matching Placebo (Drug)

Open-Label

Experimental

Part 2: ZX008 is supplied as an oral solution. Study medication will be administered twice a day (BID) in equally divided doses.

干预措施: ZX008 0.2 or 0.8 mg/kg/day (Drug)

结局指标

主要结局

Part 2: Percentage of Participants With Serious TEAEs

时间窗: From Part 2 Baseline until end of the OLE Period (up to 72 months)

A serious adverse event (SAE) was defined as any untoward medical occurrence that at any dose: Results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant.

Part 2: Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)

时间窗: From Part 2 Baseline until end of the OLE Period (up to 72 months)

An Adverse event (AE) was defined as any unfavourable and unintended sign, symptom, or disease temporally associated with the use of investigational product, or whether considered related to the investigational product. A TEAE in Part 2 was defined as any AE with an onset on or after the first dose in Part 2. AEs with onset in Part 1 that are ongoing in Part 2 were not included in the count of AEs in Part 2.

Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in the Combined Titration and Maintenance Period (T+M) in the ZX008 0.8 mg/kg/Day Group Compared to the Placebo Group

时间窗: From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]

Percent change in frequency of seizures that result in drops (DSF: drop seizure frequency) per 28 days between the combined Titration and Maintenance (T+M) and Baseline. The percent change from Baseline DSF was calculated as the change in DSF between T+M and Baseline / DSF during Baseline\* 100. The seizure types included in the count were: atonic, tonic, tonic/atonic, generalized tonic-clonic, and secondarily generalized tonic-clonic seizures resulting in drops.

次要结局

  • Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) Between Baseline and the Maintenance Period(During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percent Change From Baseline in the Frequency of Seizures That Typically Result in Drops in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Countable Motor Seizures That do Not Result in Drops(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Area Under the Concentration-time Curve of Fenfluramine and Norfenfluramine From Time Zero to Time 24 Hours [AUC0-24hours] at Steady State(At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose)
  • Part 2: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC Confirmed) in OLE Period(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver(At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months))
  • Part 1: Percentage of Participants Who Achieve a >=50% Reduction From Baseline in the Frequency of Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 2: Change From Baseline in the Frequency of All Countable Non-motor Seizures in OLE Period(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Percent Change From Baseline in the Frequency of All Countable Seizures (ESC Confirmed or Not) in OLE Period(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Change From Baseline in Duration of Longest Interval Between Seizures That Result in Drops (ESC Confirmed) in OLE Period(From Part 2 Baseline until end of the OLE Period (up to 72 months))
  • Part 1: Percent Change From Baseline in the Frequency of Seizures That Result in Drops (ESC-confirmed) in T+M in the ZX008 0.2 mg/kg/Day Group Compared to the Placebo Group(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percentage of Participants Who Achieve Improvement (Minimally, Much or Very Much Improved) in the CGI-I Scale as Assessed by Principal Investigator Comparing ZX008 0.8 and 0.2 mg/kg/Day Groups Independently Versus Placebo(At Day 99 (Visit 12))
  • Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in T+M in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Change From Baseline in the Frequency of All Countable Non-motor Seizures in the Maintenance Period in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Typically Results in Drops(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percent Change From Baseline in Frequency of All Seizures That Typically Result in Drops in T+M, Whether ESC-confirmed as Drop or Not in the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percent Change From Baseline in the Frequency of All Countable Seizures (Motor and Non-motor) in the Maintenance Period in ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percent Change From Baseline in Frequency of Countable Seizures That do Not Result in Drops (ESC Confirmed)(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <=0% Reduction), or >0, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in Seizures That Result in Drops(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Non-motor Seizures(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Duration of Longest Interval (Days) Between Seizures That Result in Drops Comparing the ZX008 0.8 mg/kg/Day and 0.2 mg/kg/Day Groups Independently Versus Placebo(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)])
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline, or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Motor Seizures(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Percentage of Participants Who Achieved a Worsening From Baseline (ie <= 0% Reduction), or >0%, >=25%, >=50%, >=75%, 100% Reduction, and "Near Seizure Freedom" Between Baseline and T+M, and Baseline and M, in All Countable Seizures(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Change From Baseline in Number of Seizure-free Days During T+M and M Period(From Baseline up to 14 weeks [Titration Period (2 weeks) + Maintenance Period (12 weeks)]; During Maintenance Period (12 weeks), compared to Baseline)
  • Part 1: Maximum Observed Plasma Concentration of Fenfluramine and Norfenfluramine Determined Directly From the Concentration Time Profile [Cmax] at Steady State(At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose)
  • Part 2: Change From Baseline in the Frequency of All Countable Seizures That Did Not Result in Drops (ESC Confirmed) in OLE Period(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Typically Result in Drops(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 1: Minimum Observed Plasma Concentration of Fenfluramine and Norfenfluramine at Steady State Determined Directly From the Concentration-time Profile [Cmin] at Steady State(At Visit 8 (Day 43) of the Maintenance Period: pre-dose, 1, 2, and 4-6 hours post-dose)
  • Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Motor Seizures(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 1: Clinical Global Impression - Improvement as Assessed by the Parent/Caregiver(At Days 15, 43, 71 and 99)
  • Part 1: Percentage of Participants With TEAEs(Baseline up to 14 weeks + Taper/Transition (2 weeks))
  • Part 1: Percentage of Participants With Serious TEAEs(Baseline up to 14 weeks + Taper/Transition (2 weeks))
  • Part 2: Percent Change From Baseline in the Frequency of All Seizures That Typically Result in Drops Between Baseline and the OLE Period Whether ESC Confirmed as Drop or Not(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Percent Change From Baseline in the Frequency of All Countable Motor Seizures in OLE Period(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of Seizures That Result in Drops (ESC Confirmed)(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Change From Baseline in Number of Seizure-free Days Per 28 Days (ESC Confirmed) in OLE Period(From Part 2 Baseline until end of OLE Period (up to 72 months))
  • Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Non-motor Seizures(From OLE Month 1 to Month12, compared to Baseline (Part 1))
  • Part 2: Clinical Global Impression - Improvement as Assessed by the Principal Investigator(At OLE Day 1, OLE Months (M) 1, 2, 3, 6, 9, 12, and Last Assessment (up to 72 months))
  • Part 2: Percentage of Participants Who Achieved a Worsening From Baseline, or > 0%, >=25%, >= 50%, >= 75%, 100% Reduction, and "Near Seizure Freedom" From Baseline in Frequency of All Countable Seizures(From OLE Month 1 to Month12, compared to Baseline (Part 1))

研究者

发起方
Zogenix International Limited, Inc., a subsidiary of Zogenix, Inc.
申办方类型
Industry
责任方
Sponsor

研究点 (72)

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