Abstracts

Rationale: Ganaxolone (GNX) is a synthetic analog of the endogenous GABA modulator allopregnanolone. GNX 1500mg/day has been shown as safe and effective for the treatment of epilepsy in a 10 wk, double-blind (DB), placebo (PBO)-controlled study of adjunctive therapy in adult outpatients with uncontrolled partial onset seizures (POS)(Tsai, J., Antiepileptic Drug Trials X, Coral Gables, FL, April 2009). A 2 year, open-label extension (OLE) to the DB study was conducted to assess the long-term safety, tolerability and efficacy of GNX. Methods: Adults (N=124) aged 18 to 69 yrs having POS with or without secondary generalization were enrolled in the OLE at 24 US sites. Subjects received GNX 1500mg/day as 500mg tid or maximally tolerated dose regardless of prior treatment in the DB study. Up to 3 concomitant AEDs at stable doses were permitted.Results: Preliminary non-cohort analysis of OLE data shows subjects experienced a reduction in mean weekly seizure frequency from baseline to endpoint of 14.2% (median 23.2%). The reduction in mean weekly seizure frequency measured at Wk 52 was 34.7% (median 43.2%). Mean weekly seizure frequency decreased by 13.9% (median 23.5%) after 10 wks of open-label treatment for the group that received PBO in the DB study and began GNX in the OLE. This result is similar to the 17.6% decrease seen with GNX treatment in the DB study. DB GNX subjects who continued on GNX in the OLE maintained their response. The overall responder rate (defined as 50% improvement over DB baseline) in the OLE was 24.2%; the rate at 52 wks was 42.6%.Conclusions: Analysis of data from a 2 year OLE of GNX for adjunctive treatment of refractory POS shows GNX maintained seizure control with extended use