{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:25:39Z","timestamp":1784046339877,"version":"3.55.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,7,10]],"date-time":"2022-07-10T00:00:00Z","timestamp":1657411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016814","name":"Marinus Pharmaceuticals, Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Patients with refractory status epilepticus (RSE) have failed treatment with benzodiazepines and \u22651\u00a0second\u2010line intravenous (IV) antiseizure medication (ASM). Guidelines recommend IV anesthesia when second\u2010line 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an open\u2010label, phase 2 trial conducted from February 19, 2018 to September 18, 2019, at three sites in the United States. Patients were aged \u226512\u2009years, had convulsive or nonconvulsive SE, and failed to respond to \u22651\u00a0second\u2010line IV ASM. Twenty\u2010one patients were screened; 17 were enrolled. Patients received IV ganaxolone added to standard\u2010of\u2010care ASMs. Ganaxolone infusion was initiated as an IV bolus (over 3\u00a0min) with continuous infusion of decreasing infusion rates for 48\u201396\u2009h followed by an 18\u2010h taper. There were three ganaxolone dosing cohorts: low, 500\u2009mg\/day; medium, 650\u2009mg\/day; and high, 713\u2009mg\/day. The primary end point was the number of patients not requiring escalation to IV anesthetic treatment within 24\u2009h of ganaxolone initiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Most of the 17 enrolled patients (65%) had nonconvulsive SE, and had failed a median of three prior ASMs, including first\u2010line benzodiazepine and second\u2010line IV ASM therapy. Median time to SE cessation following ganaxolone initiation was 5\u00a0min. No patient required escalation to third\u2010line IV anesthetics during the 24\u2010h period following ganaxolone initiation. Two treatment\u2010related serious adverse events (sedation) were reported. Of the three deaths, none was considered related to ganaxolone; all occurred 9\u201322\u2009days after completing ganaxolone.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>IV ganaxolone achieved rapid and durable seizure control in patients with RSE, and showed acceptable safety and tolerability.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17343","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T13:28:40Z","timestamp":1656077320000},"page":"2381-2391","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Intravenous ganaxolone for the treatment of refractory status epilepticus: Results from an <scp>open\u2010label<\/scp>, <scp>dose\u2010finding<\/scp>, phase 2 trial"],"prefix":"10.1111","volume":"63","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6075-247X","authenticated-orcid":false,"given":"Henrikas","family":"Vaitkevicius","sequence":"first","affiliation":[{"name":"Department of Neurology Brigham and Women's Hospital  Boston Massachusetts USA"},{"name":"Marinus Pharmaceuticals  Radnor Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. 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