title: Clinical evaluation of ganaxolone in pediatric and adolescent patients with refractory epilepsy.
abstract: OBJECTIVE
  A pilot study of the safety, tolerability, dose range and potential efficacy of ganaxolone for the treatment of refractory epilepsy in pediatric and adolescent subjects.
  
  
  METHODS
  We report the results of a nonrandomized, nonblinded, open-label, dose-escalation trial of ganaxolone in pediatric subjects (5-15 years) suffering from refractory epilepsy. Subjects received an oral suspension of ganaxolone in a 1:1 complex with beta-cyclodextrin in a dose escalation (1 mg/kg, b.i.d. to 12 mg/kg t.i.d.) schedule over 16 days. This was followed by a maintenance period for 8 weeks. Subjects that showed significant response were eligible for a compassionate use extension period.
  
  
  RESULTS
  Fifteen subjects enrolled, eight completed the trial and three continued in the open-label compassionate-use extension period. All subject exhibited refractory partial or generalized epilepsy. In an intent-to-treat analysis, four (25%) were considered substantial responders (>or=50% reduction in seizure frequency), two (13%) were considered moderate responders (between 25 and 50% reduction in seizure frequency) and the remainder were considered nonresponders (<24% reduction). Three subjects entered the extension phase, one remained essentially seizure-free for over 3.5 years of ganaxolone administration. Ganaxolone was tolerated well. A total of 17 adverse events were reported in 10 patients, all were considered mild to moderate in severity. Somnolence was the most frequently (nine) reported adverse event.
  
  
  CONCLUSIONS
  This pilot study is consistent with other clinical studies indicating that ganaxolone has anticonvulsant activity in humans. The results of this study encourage the further study of ganaxolone as an antiepileptic therapy.
authors.affiliation: Marinus Pharmaceuticals, Inc., Branford, Connecticut 06405, USA. vpieribone@marinuspharma.com
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Pieribone
authors.forename: Julia
authors.initials: J
authors.lastname: Tsai
authors.forename: Christine
authors.initials: C
authors.lastname: Soufflet
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rey
authors.forename: Ken
authors.initials: K
authors.lastname: Shaw
authors.forename: Earl
authors.initials: E
authors.lastname: Giller
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy* / Q000517:prevention & control; D005260:Female; D006801:Humans; D008297:Male; D010865:Pilot Projects; D011280:Pregnanolone / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; C105051:ganaxolone; D011280:Pregnanolone