A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intravenous Ganaxolone in Status Epilepticus
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 3
- 主要终点
- Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE
研究概览
简要总结
This study evaluated the effectiveness and safety of an investigational product (IP), intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).
详细描述
This is a double-blind, randomized, placebo-controlled study to evaluate the efficacy and safety of IV ganaxolone in status epilepticus. Investigational product was added to standard of care following failure of any two or more antiseizure medications (benzodiazepine and one IV antiepileptic drug (AED) or two IV AEDs. Participants were screened for inclusion/exclusion criteria prior to receiving investigational product by continuous IV infusion. Participants were followed for approximately 4 weeks. Participants who are known to be at risk for SE were consented or assented prior to an SE event.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant, participant's parent, guardian, or legal authorized representative (LAR) must provide signed of informed consent/assent, and once capable (per institution guidelines), there must be documentation of consent/assent by the participant demonstrating they are willing and aware of the investigational nature of the study and related procedures. Where allowed by law, where the participant lacks the capacity to make informed decisions regarding his/her medical treatment options, the treating clinician may follow their deferred consenting practices. The clinician will make the final decision based on the best interests of the particiapant.
- •Male or females 12 years of age and older at the time of the first dose of IP
- •SE meeting the following criteria:
- •a. A diagnosis of SE with or without prominent motor features based on clinical and EEG findings:
- •i. Diagnosis is established by:
- •For SE with prominent motor features: Clinical and EEG seizure activity indicative of convulsive, myoclonic or focal motor SE.
- •For SE without prominent motor features (nonconvulsive SE): Appropriate clinical features and an EEG indicative of non-convulsive status epilepticus (NCSE)
- •ii. For any type of SE:
- •At least 6 minutes of cumulative seizure activity over a 30-minute period within the hour before IP initiation, AND
- •Seizure activity during the 30 minutes immediately prior to IP initiation
- •b. The treating clinician(s) anticipate that IV anesthesia is likely to be the next treatment for SE that persists following initiation of IP
- •Participants must have received any two or more of the following agents for treatment of the current episode of SE administered at an adequate dose and for a sufficient duration, in the judgment of the investigator, to demonstrate efficacy
- •Benzodiazepines,
- •IV Fosphenytoin/phenytoin,
- •IV Valproic acid,
- •IV Levetiracetam,
- •IV Lacosamide,
- •IV Brivaracetam, or
- •IV Phenobarbital
- •Body mass index (BMI) < 40 or, if BMI is not able to be calculated at screening, participant is assessed by investigator as not morbidly obese
排除标准
- •Life expectancy of less than 24 hours
- •Anoxic brain injury or an uncorrected rapidly reversable metabolic condition as the primary cause of SE (e.g., hypoglycemia < 50 milligram per deciliter [mg/dL] or hyperglycemia > 400 mg/dL)
- •Participants who have received high-dose IV anesthetics (e.g., midazolam, propofol, thiopental, or pentobarbital) during the current episode of SE for more than 18 hours, or who continue to have clinical or electrographic evidence of persistent seizures while receiving high-dose IV anesthetics.
- •Clinical condition or advance directive that would NOT permit use of IV anesthesia
- •Participants known or suspected to be pregnant
- •Participants with known allergy or sensitivity to progesterone or allopregnanolone medications/supplements
- •Receiving a concomitant IV product containing Captisol®
- •Known or suspected hepatic insufficiency or hepatic failure leading to impaired synthetic liver function.
- •Known or suspected stage 3B (moderate to severe; estimated glomerular filtration rate [eGFR] 44-30 milliliter/minutes/1.73-meter square [mL/min/1.73m^2]), stage 4 (severe; eGFR 29-15 mL/min/1.73m^2), or stage 5 (kidney failure; eGFR < 15 mL/min/1.73m^2 or dialysis) kidney disease
- •Use of an investigational product for which less than 30 days or 5 half-lives have elapsed from the final product administration. Participation in a non-interventional clinical study does not exclude eligibility.
研究组 & 干预措施
IV Placebo
Placebo bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
干预措施: Placebo (Drug)
IV ganaxolone active
Ganaxolone bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
干预措施: Ganaxolone (Drug)
结局指标
主要结局
Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE
时间窗: Up to 30 minutes
SE cessation was determined by the investigator based on clinical and electroencephalography (EEG). Medications for the acute treatment of SE were defined as antiepileptic drugs (AEDs) administered to abort ongoing SE or prevent imminent recurrence of SE based on clinical or EEG evidence.
Percentage of Participants With no Progression to Intravenous (IV) Anesthesia for 36 Hours Following Investigational Product (IP) Initiation
时间窗: Up to 36 hours after IP initiation
Percentage of participants with no progression to IV anesthesia for 36 hours following IP initiation SE cessation was based on investigator report with confirmation by assessment of concomitant medication data.
Number of Participants With Treatment Emergent Adverse Events
时间窗: Up to 4 weeks after IP initiation
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant who has been administered a pharmaceutical product; it does not necessarily have a causal relationship with this treatment. Treatment-emergent adverse event (TEAE) is defined as an AE that occurred or worsened at the time of or following IP initiation.
次要结局
- Time to SE Cessation Following IP Initiation(Up to 72 hours after IP initiation)
- Percentage of Participants With no Progression to IV Anesthesia for 72 Hours Following IP Initiation(Up to 72 hours after IP initiation)
- Percentage of Participants With Any Escalation of Treatment in the First 24 Hours Following IP Initiation(Up to 24 hours after IP initiation)
- Time to Treatment Escalation in the First 24 Hours Following IP Initiation(Up to 24 hours after IP initiation)
- Time to Initiation of Anesthesia for SE Treatment Through the Final Study Follow-up Visit/Contact(Up to 4 Weeks following IP initiation)
- Percentage of Participants Who Develop Super Refractory Status Epilepticus (SRSE) Through the Final Study Follow-up Visit/Contact(Up to 4 Weeks following IP initiation)
- Percent Change From Baseline in Seizure Burden Through 72 Hours Following IP Initiation(Up to 72 hours after IP initiation)