Efficacy and safety of ezogabine/retigabine as adjunctive therapy to specified single antiepileptic medications in an open-label study of adults with partial-onset seizures

Abstract Purpose To assess efficacy/tolerability of ezogabine (EZG)/retigabine (RTG) in combination with specified monotherapy antiepileptic drug (AED) treatments in adults with uncontrolled partial-onset seizures using a flexible dosing regimen. Methods NCT01227902 was an open-label, uncontrolled study of flexibly dosed EZG/RTG. Adults with partial-onset seizures must have been taking either carbamazepine/oxcarbazepine (CBZ/OXC), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA). The study comprised a screening/baseline phase, a 4-week titration phase (initiation on 150mg/day [50mg three times daily (TID)] with weekly increases of 150mg/day [50mg TID] over 4 weeks to 600mg/day), and a flexible dose evaluation (FDE) phase (optional weekly dose changes of 50–150mg/day, to an optimal daily dosage [300–1200mg/day]). The primary efficacy endpoint was percentage of patients experiencing a ≥50% reduction from baseline in partial seizure frequency (responder rate) during the treatment phase (titration and FDE phases). Safety and tolerability were also assessed. Results Patients ( N =203) were enrolled and received ≥1 dose of EZG/RTG. The dose of EZG/RTG prescribed most frequently during the treatment phase was 600mg/day for all AED groups. Responder rates during the treatment phase were: 40.0% (CBZ/OXC), 32.0% (LTG), 50.0% (LEV), and 56.9% (VPA). Treatment-emergent adverse events occurred in 82% (CBZ/OXC), 76% (LTG), 73% (LEV), and 67% (VPA) of patients; most were of mild-to-moderate intensity. Conclusions EZG/RTG was effective as adjunctive therapy to CBZ/OXC, LTG, LEV, and VPA, using a flexible dosing regimen, in adults with partial-onset seizures; safety and tolerability were consistent with that previously observed.