An Open-Label Study To Determine Safety, Tolerability And Efficacy Of Long -Term Oral Lacosamide (LCM) As Adjunctive Therapy In Children With Epilepsy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 366
- 试验地点
- 69
- 主要终点
- Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
研究概览
简要总结
SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy.
详细描述
SP848 is an open-label study to evaluate long-term safety, tolerability, and efficacy in children with epilepsy treated with Lacosamide (LCM) oral solution (syrup) or LCM tablets as adjunctive therapy. In addition, the study is designed to provide continued availability of LCM to subjects who have completed the SP847 (NCT00938431) study and to subjects who have discontinued from SP847 (NCT00938431) and who, in the investigator's opinion, would benefit from long-term administration of LCM.
SP848 will be open to subjects who have participated in other LCM pediatric clinical studies in epilepsy and will also be open to up to 100 subjects enrolling directly into SP848. Permissible LCM doses in SP848 are between 2-12 mg/kg/day (oral solution [syrup]) or the corresponding tablet dose up to a maximum dose of 600 mg/day.
Subjects enrolled in SP848 have the option of remaining on the oral solution formulation of LCM or switching to the commercial tablet formulation, if feasible.
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
- 1 Month 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •A signed informed consent form has been obtained from the parent/legal guardian and assent has been obtained from the subject, as required
- •Subject and caregiver (which may be a parent, legal guardian, or other delegated caregiver) are willing and able to comply with all study requirements, including maintaining a daily seizure diary
- •Subjects who have participated in SP847 or other lacosamide (LCM) pediatric clinical studies in epilepsy must fulfill the following inclusion criteria:
- •Subject has completed SP847 (or the subject discontinued SP847 due to a dose reduction or status epilepticus) for the treatment of uncontrolled partial-onset seizures, or subject has participated in other LCM pediatric clinical studies in epilepsy
- •Subject is expected to benefit from participation, in the opinion of the investigator
- •Subjects who enroll directly into SP848 without previous participation in a LCM clinical study must fulfill the following inclusion criteria:
- •Subject is >=4 years to <=17 years of age
- •Subject has a diagnosis of epilepsy with partial-onset seizures
- •Subject has been observed to have uncontrolled partial-onset seizures after an adequate course of treatment (in the opinion of the investigator) with at least 2 Antiepileptic Drugs (AEDs) (concurrently or sequentially)
- •Subject has been observed to have at least 2 countable seizures in the 4 week period prior to Screening
- •Subject is on a stable dosage regimen of 1 to 3 AEDs
- •Subject is an acceptable candidate for venipuncture
排除标准
- •Subject is receiving any investigational drugs or using any experimental devices in addition to Lacosamide (LCM)
- •Subject >= 6 years of age has a lifetime history of suicide attempt, or has suicidal ideation in the past 6 months
- •Subjects who have participated in SP847 or other LCM pediatric clinical studies in epilepsy are not permitted to enroll in the study if any of the following criteria are met:
- •Subject meets either of the following:
- •Withdrawal criteria for the primary study (with the exception of subjects who discontinued due to a dose reduction or status epilepticus). For subjects entering from EP0060, if the subject (or legal guardian) withdraws consent solely due to route of LCM administration (iv) or if the subject requires more than 10 iv LCM infusions, the subject may be allowed to participant in SP848 after discussion with and agreement from the Medical Monitor
- •Ongoing serious Adverse Event (SAE)
- •Subjects who enroll directly into SP848 without previous participation in a LCM clinical study are not permitted to enroll in the study if any of the following criteria are met:
- •Subject has ever received LCM
- •Subject has any medical or psychiatric 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 medical condition that could reasonably be expected to interfere with drug absorption, distribution, metabolism, or excretion
- •Subject has a known hypersensitivity to any component of the investigational medicinal product
- •Subject is a female of childbearing potential and does not practice an acceptable method of contraception for the duration of the study
- •Subject has a creatinine clearance less than 30mL/min
- •Subject has a clinically relevant ECG abnormality, in the opinion of the principal investigator (ie, second or third degree heart block at rest or a QT prolongation greater than 450ms)
- •Subject has hemodynamically significant heart disease (eg, heart failure)
- •Subject has an arrhythmic heart condition requiring medical therapy
- •Subject has a known history of severe anaphylactic reaction or serious blood dyscrasias
- •Subject has nonepileptic events, including psychogenic seizures, that could be confused with seizures. If both epileptic and nonepileptic events are present, epileptic events must be distinguished from nonepileptic phenomena
- •Subject has a history of primary generalized epilepsy
- •Subject is taking monoamine oxidase inhibitors-A (MAOI-A) or narcotic analgesics.
- •Subject has epilepsy secondary to a progressing cerebral disease or any other progressively neurodegenerative disease, such as Rasmussen syndrome
- •Subject has a known sodium channelopathy, such as Brugada syndrome
- •Subject has >2x upper limit of normal (ULN) of any of the following: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or >ULN total bilirubin (1.5xULN total bilirubin if known Gilbert's syndrome). If subject has elevations only in total bilirubin that are >ULN and <1.5xULN, fractionate bilirubin to identify possible undiagnosed Gilbert's syndrome (ie, direct bilirubin <35%)
- •Subjects who were directly enrolled in EP0060 for iv LCM replacement therapy or to initiate LCM treatment are not permitted to enroll in the study if any of the following criteria are met:
- •Subjects have previously participated in a long-term, open-label LCM study
研究组 & 干预措施
Lacosamide
Subjects and their caregivers may chose to receive Lacosamide oral solution (syrup) or Lacosamide tablets. The maximum duration of LCM administration will be approximately 2 years.
干预措施: Lacosamide (Drug)
结局指标
主要结局
Number of Participants With At Least One Treatment-Emergent Adverse Event (TEAE)
时间窗: From Baseline to End of Safety Follow-Up (up to 4.3 years)
An AE is any untoward medical occurrence in a participant or clinical investigation study participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.
Number of Participants That Withdraw Due to a Treatment-Emergent Adverse Event
时间窗: From Baseline to End of Safety Follow-Up (up to 4.3 years)
TEAEs were defined as those events which started on or after the date of first SP848 LCM administration and occurred within 30 days after last dose of LCM, or whose severity worsened on or after the date of first SP848 LCM administration.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: From Baseline to End of Safety Follow-Up (up to 4.3 years)
SAE was any untoward medical occurrence that at any dose resulted in death, is life-threatening, required in participant hospitalization or prolongation of existing hospitalization, is a congenital anomaly or birth defect, is an infection that requires treatment with parenteral antibiotics, other important medical events which based on medical or scientific judgement may jeopardize the participants, or may require medical or surgical intervention to prevent any of the above.
次要结局
- Percentage of Participants With ≥75% Reduction in 28-day Partial-onset Seizure Frequency(From Baseline to End of Treatment Period (up to 4.2 years))
- Percent Change From Baseline in 28 Day Partial-onset Seizure Frequency to the End of the Treatment Period(From Baseline to End of Treatment Period (up to 4.2 years))
- Percentage of Participants Who Achieved a Seizure-free Status(From Baseline to End of Treatment Period (up to 4.2 years))
- Percentage of Participants With ≥50% Reduction in 28-day Partial-onset Seizure Frequency(From Baseline to End of Treatment Period (up to 4.2 years))
- Number of Seizure Days Per 28 Days for Participants With Generalized Seizures(Weeks 4, 8, 12, 20, 28, 36, 44, 52, 60, 72, 84 and 96)