Intravenous Ganaxolone as Adjunctive Therapy to Treat Subjects With Status Epilepticus

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the effectiveness and safety of an investigational drug, IV ganaxolone, as adjunctive therapy to standard of care to treat subjects with status epilepticus.

Detailed Description
-----------------
This is a double-blind, randomized, placebo-controlled study to evaluate the safety, tolerability, and efficacy of adjunctive IV ganaxolone in subjects with SE. Study drug will be added to standard of care before IV anesthetic during the treatment of SE. Subjects will be screened for inclusion/exclusion criteria prior to receiving study drug as adjunctive therapy by continuous IV. Subject's will be followed up for 3 weeks post-treatment. Subjects who are known to be at risk for SE may be consented and/or assented prior to an SE event.

Official Title
-----------------
A Double-Blind Randomized, Placebo Controlled Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of Intravenous Ganaxolone as Adjunctive Therapy to Treat Subjects With Status Epilepticus

Conditions
-----------------
Status Epilepticus, Convulsive Status EPILEPTICUS, Non Convulsive Status Epilepticus, Epilepsy

Intervention / Treatment
-----------------
* Drug: IV Ganaxolone active
* Drug: IV Placebo, non-active


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects 12 years of age and older Clinical and/or electrographic seizures Exclusion Criteria: Life expectancy of less than 24 hours Anoxic brain injury as primary cause of SE Recent (<24 hour) traumatic brain injury as the primary cause of SE Administered anesthesia for the treatment of SE

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Double-blind study that will randomize subjects to ganaxolone or placebo in a 1:1 ratio as adjunctive therapy to their standard of care.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV Ganaxolone active<br>Ganaxolone IV loading dose with continuous infusion (maintenance dose) for 2-4 days followed by an 18-hour taper. | Drug: IV Ganaxolone active<br>* IV<br>|
| Placebo Comparator: IV Placebo, non-active<br>Placebo IV loading dose with continuous infusion (maintenance dose) for 2-4 days followed by an 18-hour taper. | Drug: IV Placebo, non-active<br>* IV<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Did Not Require an IV Anesthetic Drug for SE Treatment | Number of participants who did not require an intravenous (IV) Anesthetic Drug (a third-line Treatment) for Status Epilepticus (SE) within the first 24 hours after Study Drug Initiation. | 24 hours post study drug initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Cessation of SE | Summary of Time to SE Cessation | Time to SE Cessation, assessed up to 24 hours | 
| Number of Participants Who Required No Escalation of Treatment for Ongoing or Recurrent SE | Number of participants who Required No Escalation of Treatment for Ongoing or Recurrent SE | Drug initiation through follow-up period, up to approximately 4 weeks | 
| Number of Participants With No SE Recurrence Per Principal Investigator | Number of participants with No SE Recurrence per Principal Investigator within 24hrs of starting treatment, during treatment period (excluding taper), during taper, during 24-hr follow-up period, and during follow-up period. | Baseline (within 24hrs of treatment) through follow up period, up to approximately 4 weeks. | 
| Seizure Burden | Seizure Burden (%) Baseline and Percentage Change from Baseline by Time Point | Baseline (Pre-dose) to <-24hrs (Post Dose) |