A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intravenous Ganaxolone in Status Epilepticus
Overview
- Phase
- Phase 3
- Intervention
- Placebo
- Conditions
- Status Epilepticus
- Sponsor
- Marinus Pharmaceuticals
- Enrollment
- 100
- Locations
- 3
- Primary Endpoint
- Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
This study evaluated the effectiveness and safety of an investigational product (IP), intravenous (IV) ganaxolone, to treat participants with status epilepticus (SE).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
IV Placebo
Placebo bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
Intervention: Placebo
IV ganaxolone active
Ganaxolone bolus dose followed by continuous infusion for 36 hours, followed by 12 hour taper
Intervention: Ganaxolone
Outcomes
Primary Outcomes
Percentage of Participants With SE Cessation Within 30 Minutes of Investigational Product (IP) Initiation Without Medications for the Acute Treatment of SE
Time Frame: 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
Time Frame: 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
Time Frame: 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.
Secondary Outcomes
- 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)