Skip to main content
Journal cover image

Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial.

Publication ,  Journal Article
Vaitkevicius, H; Ramsay, RE; Swisher, CB; Husain, AM; Aimetti, A; Gasior, M
Published in: Epilepsia
September 2022

OBJECTIVE: Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and ≥1 second-line intravenous (IV) antiseizure medication (ASM). Guidelines recommend IV anesthesia when second-line ASMs have failed, but potential harms can outweigh the 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. METHODS: This was an open-label, phase 2 trial conducted from February 19, 2018 to September 18, 2019, at three sites in the United States. 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 min) with continuous infusion of decreasing infusion rates for 48-96 h followed by an 18-h taper. There were three ganaxolone dosing cohorts: low, 500 mg/day; medium, 650 mg/day; and high, 713 mg/day. The primary end point was the number of patients not requiring escalation to IV anesthetic treatment within 24 h of ganaxolone initiation. RESULTS: Most of the 17 enrolled patients (65%) had nonconvulsive SE, and had failed a median of three prior ASMs, including first-line benzodiazepine and second-line IV ASM therapy. Median time to SE cessation following ganaxolone initiation was 5 min. No patient required escalation to third-line IV anesthetics during the 24-h period following ganaxolone initiation. Two treatment-related serious adverse events (sedation) were reported. Of the three deaths, none was considered related to ganaxolone; all occurred 9-22 days after completing ganaxolone. SIGNIFICANCE: IV ganaxolone achieved rapid and durable seizure control in patients with RSE, and showed acceptable safety and tolerability.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Epilepsia

DOI

EISSN

1528-1167

Publication Date

September 2022

Volume

63

Issue

9

Start / End Page

2381 / 2391

Location

United States

Related Subject Headings

  • Status Epilepticus
  • Pregnanolone
  • Neurosteroids
  • Neurology & Neurosurgery
  • Humans
  • Benzodiazepines
  • Anticonvulsants
  • Anesthetics
  • 3209 Neurosciences
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Vaitkevicius, H., Ramsay, R. E., Swisher, C. B., Husain, A. M., Aimetti, A., & Gasior, M. (2022). Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial. Epilepsia, 63(9), 2381–2391. https://doi.org/10.1111/epi.17343
Vaitkevicius, Henrikas, R Eugene Ramsay, Christa B. Swisher, Aatif M. Husain, Alex Aimetti, and Maciej Gasior. “Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial.Epilepsia 63, no. 9 (September 2022): 2381–91. https://doi.org/10.1111/epi.17343.
Vaitkevicius H, Ramsay RE, Swisher CB, Husain AM, Aimetti A, Gasior M. Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial. Epilepsia. 2022 Sep;63(9):2381–91.
Vaitkevicius, Henrikas, et al. “Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial.Epilepsia, vol. 63, no. 9, Sept. 2022, pp. 2381–91. Pubmed, doi:10.1111/epi.17343.
Vaitkevicius H, Ramsay RE, Swisher CB, Husain AM, Aimetti A, Gasior M. Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an open-label, dose-finding, phase 2 trial. Epilepsia. 2022 Sep;63(9):2381–2391.
Journal cover image

Published In

Epilepsia

DOI

EISSN

1528-1167

Publication Date

September 2022

Volume

63

Issue

9

Start / End Page

2381 / 2391

Location

United States

Related Subject Headings

  • Status Epilepticus
  • Pregnanolone
  • Neurosteroids
  • Neurology & Neurosurgery
  • Humans
  • Benzodiazepines
  • Anticonvulsants
  • Anesthetics
  • 3209 Neurosciences
  • 3202 Clinical sciences