Abstracts

Retigabine (RGB) has a novel mode of action and exhibits potent anticonvulsant activity in broad range of animal models of epilepsy. It potentiates GABA-evoked currents and enhances K⁺ current mediated by human KCNQ2 and KCNQ3 potassium channels. This study evaluated the efficacy and safety of RGB administered as adjunctive therapy to patients with refractory partial-onset seizures. All patients who participated and completed a double blind placebo controlled study were invited to participate in an open label long-term extension study. During the double blind portion of the study, patients received placebo, 200 mg, 300 mg or 400 mg of RGB three times daily (tid). At the end of the study, all patients were converted to receive 300 mg tid of RGB. Following this, each patient[apos]s daily dose of RGB or concomitant AEDs could be either reduced or increased. The maximum daily dose of RGB allowed was 1,200 mg. Each patient maintained a daily seizure diary. Patients were followed-up at regular intervals and efficacy and safety parameters (AEs, ECG, hematology, biochemistry and urinalysis) were assessed. Of the 399 patients enrolled in the double blind study, 279 completed the study and 222 enrolled in the open label study. Of these, 18 (8%) discontinued within the first three months and 41 (18%) discontinued within six-months. The most common daily dose of RGB was 900 mg (105 patients; 47.3 %) and only a minority of the patients titrated the dose to 1,200 mg (53; 23.4 %). The median decrease in monthly total partial seizure frequency from baseline was 48.3 %. 103 patients (46.4%) showed a reduction in monthly total partial seizure frequency of [ge] 50 %. The most common cause for discontinuation from the study was adverse events related to CNS. There were no clinically significant changes in ECGs or laboratory parameters. RGB appears to be safe, efficacious and well tolerated. RGB has demonstrated a meaningful reduction in total partial seizure frequency. The Phase III clinical development program for RGB will further evaluate the efficacy and tolerability of this novel AED.