Intravenous Ganaxolone for the Treatment of Refractory Status Epilepticus: Results from an Open‐Label, Dose‐Finding, Phase 2 Trial



Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) anti-seizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh benefits. Novel treatments are needed to stop and durably control RSE without escalation to IV anesthetics. Ganaxolone is an investigational neuroactive steroid in development for RSE treatment. This study’s objective was to determine the appropriate dosing for IV ganaxolone in RSE and obtain a preliminary assessment of efficacy and safety.


This was an open-label, phase 2 trial conducted 19FEB2018 to 18SEPT2019 at three sites in the US. Patients were aged ≥12 years, had convulsive or nonconvulsive SE, and failed to respond to ≥1 second-line IV ASM. Twenty-one patients were screened; 17 were enrolled. Patients received IV ganaxolone added to standard-of-care ASMs. Ganaxolone infusion was initiated as an IV bolus (over 3 minutes) with continuous infusion of decreasing infusion rates for 48–96 hours followed by an 18-hour taper. There were three ganaxolone dosing cohorts (low, 500 mg/day; medium, 650 mg/day; high, 713 mg/day). The primary endpoint was the number of patients not requiring escalation to IV anesthetic treatment within 24 hours of ganaxolone initiation.


Most of the 17 enrolled patients (65%) had nonconvulsive SE, and had failed a median of 3 prior ASMs, including first-line benzodiazepine and second-line IV ASM therapy. Median time to SE cessation following ganaxolone initiation was 5 minutes. No patient required escalation to third-line IV anesthetics during the 24-hour period following ganaxolone initiation. Two treatment-related serious adverse events (sedation) were reported. Of the 3 deaths, none was considered related to ganaxolone; all occurred 9–22 days after completing ganaxolone.


IV ganaxolone achieved rapid and durable seizure control in patients with refractory status epilepticus, and showed, acceptable safety and tolerability.