Assessment of ganaxolone's anticonvulsant activity using a randomized, double-blind, presurgical trial design. Ganaxolone Presurgical Study Group.
OBJECTIVE
A double-blind, randomized, placebo-controlled clinical trial to examine the safety, tolerability, and antiepileptic activity of ganaxolone in patients after withdrawal from other antiepileptic drugs during presurgical evaluations was performed.


METHODS
Fifty-two eligible patients were withdrawn from antiepileptic drugs and randomized to receive ganaxolone (24 patients) or placebo (28 patients) for up to 8 days. Ganaxolone was administered at a dose of 1500 mg/d on day 1 and 1875 mg/d on days 2 to 8. Dosing occurred three times per day: immediately after breakfast, lunch, and dinner.


RESULTS
The primary measure of antiepileptic activity was duration of treatment before withdrawal from the trial. Kaplan-Meier curves depicted a clear separation between treatment groups, with 50% of the ganaxolone-treated patients completing the entire study, compared with 25% of patients treated with placebo. Intent-to-treat survival analyses revealed a trend toward efficacy with ganaxolone (p = 0.0795, log rank test). Covariate analyses revealed a significant treatment effect on survival time in men (p = 0.03). Post-hoc chi2 probe analyses focusing on patients who completed the entire study revealed a significant difference (p = 0.04) between treatment groups. The tolerability of ganaxolone was similar to that of placebo, with adverse events being reported by 79% of patients in the ganaxolone group and 68% of patients in the placebo group.


CONCLUSIONS
Ganaxolone monotherapy was well tolerated for the duration of this clinical trial, and the results provide preliminary evidence that ganaxolone does have antiepileptic activity.
Laxer
K
K
Northern California Comprehensive Epilepsy Center, San Francisco, USA.
Blum
D
D
Abou-Khalil
B W
BW
Morrell
M J
MJ
Lee
D A
DA
Data
J L
JL
Monaghan
E P
EP
D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011280:Pregnanolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome; D014635:Valproic Acid / Q000627:therapeutic use
D000927:Anticonvulsants; D010919:Placebos; D014635:Valproic Acid; C105051:ganaxolone; D011280:Pregnanolone