A Multicenter, Open-Label, Randomized, Active Comparator Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Lacosamide in Neonates With Repeated Electroencephalographic Neonatal Seizures
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 29
- 试验地点
- 18
- 主要终点
- Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of lacosamide (LCM) versus an Active Comparator chosen based on standard of care (StOC) in severe and nonsevere seizure burden (defined as total minutes of electroencephalographic neonatal seizures (ENS) per hour) in neonates with seizures that are not adequately controlled with previous anti-epileptic drug (AED) treatment.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- — 至 28 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥34 weeks of corrected gestational age (CGA), <46 weeks of CGA, and <28 days of postnatal age (PNA)
- •Participants who have confirmation on video-electroencephalogram (EEG) of ≥2 minutes of cumulative electroencephalographic neonatal seizures (ENS) or ≥3 identifiable ENS prior to entering the Treatment Period
- •Participants must have received either phenobarbital (PB), levetiracetam (LEV), or midazolam (MDZ) (in any combination) before entering the study
- •Participant weighs at least 2.3 kg at the time of enrollment Informed consent
- •An Independent Ethics Committee (IEC)-approved written informed consent form (ICF) is signed and dated by the participant's parent(s) or legal representative(s)
排除标准
- •Participant with seizures responding to correction of metabolic disturbances (hypoglycemia, hypomagnesemia, or hypocalcemia) or with seizures for which a targeted, known treatment is available
- •Participant has seizures related to prenatal maternal drug use or drug withdrawal
- •Participant has a clinically relevant electrocardiogram (ECG) abnormality, in the opinion of the investigator
- •Participant receiving treatment with phenytoin (PHT), lidocaine (LDC), or other sodium channel blockers at any time
研究组 & 干预措施
Lacosamide
Study participants randomized to this arm will receive lacosamide (LCM) as an intravenous infusion in the Treatment Period and may continue to receive lacosamide in the Extension Period. Participants should be switched to oral dosing of LCM as soon as medically possible during the Extension Period.
干预措施: Lacosamide intravenous (Drug)
Lacosamide
Study participants randomized to this arm will receive lacosamide (LCM) as an intravenous infusion in the Treatment Period and may continue to receive lacosamide in the Extension Period. Participants should be switched to oral dosing of LCM as soon as medically possible during the Extension Period.
干预措施: Lacosamide oral (Drug)
Active Comparator
Study participants randomized to this arm will receive Active Comparator chosen based on standard of care (StOC) in the Clinical Practice in the Treatment Period and may continue to receive in the Extension Period.
干预措施: Active Comparator (Other)
结局指标
主要结局
Change in Seizure Burden Measured in the Evaluation Video-electroencephalogram (Video-EEG) Compared With the Baseline Video-EEG
时间窗: During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline
Baseline seizure burden was defined as seizure burden measured on the continuous video-EEG (total electroencephalographic neonatal seizures (ENS) in minutes per hour) during a period of up to 2 hours immediately prior to the first administration of study drug. An ENS was defined as an EEG seizure lasting for at least 10 seconds on video-EEG. The seizure burden in the Evaluation Period was calculated as the total duration of seizures between 1 and 3 hours after the first dose of study medication divided by the duration of interpretable video-EEG available in the same period. Change in seizure burden measured in the Evaluation video-EEG compared with the Baseline video-EEG was analyzed such that a positive value indicates a reduction in seizure burden from baseline.
次要结局
- Percentage of Responders in the Evaluation Video-EEG Compared With the Baseline Video-EEG(During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline)
- Time to Response Across the 48-hour Treatment Period Compared With the Baseline Video-EEG(Across the first 48 hours of Treatment Period, compared to Baseline)
- Time to Seizure Freedom Across the First 48-hour Treatment Period Compared With the Baseline Video-EEG(Across the first 48 hours of Treatment Period, compared to Baseline)
- Percentage of Participants With at Least 80% Reduction in Seizure Burden in the Evaluation a Video-EEG Compared With the Baseline Video-EEG(During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline)
- Percentage of Responders at the End of the First 48-hours of the Treatment Period(Across the first 48 hours of Treatment Period)
- Percentage of Study Participants Who Are Seizure-free (100% Reduction in Seizure Burden From Baseline) at 24 Hours After Start of the Treatment Period, Categorized by Study Participants With Non Severe or Severe Seizure Burden at Baseline(24 hours after the start of Treatment Period, compared to Baseline)
- Absolute Change in Seizure Burden Across the First 48-hours of the Treatment Period Measured by Continuous Video-EEG Compared With the Baseline Video-EEG(Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline)
- Percent Change in Seizure Burden Across the First 48-hours of the Treatment Period Measured by Continuous Video-EEG Compared With the Baseline Video-EEG(Treatment Period: 7-8 hours, 15-16 hours, 23-24 hours, 31-32 hours, 39-40 hours, 47-48 hours, compared to Baseline)
- Categorized Percentage of Participants With Change in Seizure Burden in the Evaluation Video-EEG Compared With the Baseline Video-EEG(During 2-hour Evaluation starting 1 hour after initial treatment (up to 2 hours), compared to Baseline)
- Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) as Reported by the Investigator(From first administration of study treatment to the End of Safety Follow-up Period (up to Day 42))
- Percentage of Participants With Treatment-emergent Marked Abnormalities in 12-lead Electrocardiogram (ECG)(Active Comparator: Screening; Lacosamide: Screening, 1-6 hours, 48 and 96 hours)
- Serum Concentration of Lacosamide(Day 1: 30-90 minutes and 6 - 8 hours after start of first infusion, 30 - 90 minutes and 6 - 8 hours after start of second or third infusion, Days 2, 3 and 4)