Abstracts

Retigabine (RGB) enhances K⁺ currents mediated by human KCNQ2 and KCNQ3 potassium channels and exhibits potent anticonvulsant activity in broad range of animal models of epilepsy. This study was designed to determine the dose range, safety, tolerability and preliminary efficacy of retigabine. 60 patients, with partial or generalized seizure disorders, who were receiving either valproic acid, topiramate, phenytoin or carbamazepine were included in this open label study. Retigabine (100-200 mg/day p.o.) was initiated in a bid or tid regimen. The dose was increased by 50-200 mg/day every one-two weeks, as tolerated, over 28-56 days. The maximum dose allowed was 1600 mg. Once the patient reached the maximum tolerated dose, it was maintained for 14 days. The patient could be tapered off their previous AED to achieve retigabine monotherapy or left on combination therapy. All patients could enter a long-term open label extension study. Forty-two (70%) patients received their RGB dose in a bid regimen and 11 (18%) in a tid regimen throughout the study; the remaining 7 (12%) received a combination of bid and tid dosing regimen. Twenty-seven patients achieved retigabine monotherapy for at least 10 days. The maximum tolerated dose of retigabine was 1100-1200 mg/day. The mean duration of retigabine therapy was 92 days. Ten (17%) patients discontinued from the study; eight due to adverse events. The most commonly reported adverse events were dizziness, asthenia, somnolence, nausea, speech disorder and tremor; dizziness and somnolence were dose limiting. Similar types of AEs were reported across different dose regimens. There was a slightly lower incidence of AEs among patients who received retigabine in a TID dose regimen compared with those patients who received a BID dose regimen (91% and 100%, respectively). The median seizure rate per 28 days was 8.1 at baseline and 6.4 during treatment. 44% of patients were found to be responders ([ge] 50% reduction in seizure frequency). Retigabine was well tolerated up to a daily dose of 1200 mg/day when administered as a bid or tid regimen in combination with other AEDs or as monotherapy and caused a reduction in seizure frequency. (Supported by Valeant Pharmaceuticals.)