Abstracts

Retigabine is a novel antiepileptic drug (AED) that enhances the potassium currents mediated by human KCNQ2/3 and KCNQ3/5 potassium channels and exhibits potent anticonvulsant activity in a broad spectrum of epilepsy animal models. The safety and efficacy of retigabine in refractory partial-onset seizures has been previously reported [1]. This report provides a descriptive analysis evaluating the efficacy of retigabine on complex partial seizures (CPS) in patients with refractory partial-onset epilepsy., 399 patients with partial-onset seizures (age range: 16-70 years, baseline seizure frequency: [underline][gt][/underline]4 seizures/month) participated in a multicenter, randomized, double-blind, placebo-controlled phase 2 trial. Study design included an 8-week baseline phase and 16-week double-blind treatment period (8-week forced titration and 8-week maintenance). Patients received either placebo or retigabine 600, 900, or 1200 mg/day and up to 2 approved AEDs. The primary efficacy variable was percent change from baseline in monthly total partial-seizure frequency. The percent change in monthly seizure rate for seizure types was considered as a secondary endpoint. Of 396 patients included in the efficacy analysis, 344 (86.9%) had CPS. 103 (26%) patients had simple partial seizures without secondary generalization (SPS)., Retigabine produced a linear dose-dependent reduction in monthly total partial-seizure frequency of 23%, 29% ([italic]p[/italic]=0.043), and 35% ([italic]p[/italic][lt]0.001) for retigabine 600, 900, and 1200 mg/day, respectively, versus 13% for placebo. Looking at the most common seizure subtype, monthly CPS frequency was also significantly reduced. Median monthly CPS rate was reduced by 29.8% ([italic]p[/italic]=0.062), 26.5% ([italic]p[/italic]=0.064), and 40.0% ([italic]p[/italic]=0.002) for retigabine 600, 900, and 1200 mg/day, respectively, versus 14.8% for placebo. Monthly median SPS rate was reduced by 23.2% ([italic]p[/italic]=0.66), 34% ([italic]p[/italic]=0.77), and 37.6% ([italic]p[/italic]=0.15) for retigabine 600, 900, and 1200 mg/day, respectively, versus 15.2% for placebo., While retigabine is effective in reducing monthly total partial-onset seizures at 900 and 1200 mg/day, it appears to be effective in reducing the rate of complex partial seizures in all doses tested. Similar numerical trends for SPS frequency were observed but sample sizes are too small to draw a conclusion. Retigabine is currently undergoing global phase 3 studies as adjunctive treatment for partial-onset seizures in adults with refractory epilepsy.
Reference
1. Porter P, Alves W, Nohria V, et al. World Congress of Neurology, 2005 (Sydney, Australia)., (Supported by Valeant Pharmaceuticals International.)