Abstracts

Retigabine (RGB) is currently under development as an adjunctive therapy for the treatment of partial-onset seizures. This study was designed to compare 3 different rates of dose titration to achieve the target dose of 1200 mg/day when administered to patients with partial onset seizures who were already taking one or two other anti-epileptic treatments. This randomized, double-blind study consisted of starting the patients on 300 mg/day of RGB administered in 3 divided doses. A total of 73 patients were randomized to one of 3 titration groups: 24 in the 150 mg/2 days group, 25 in the 150 mg/4 days group, and 24 in the 150 mg/7 days group achieving the target dose of 1200 mg/day on day 13, 25 and 43, respectively. The discontinuation rates in the fast- and medium-titration groups were compared with the discontinuation rates in the slow-titration group as a measure of the tolerability of different titration rates. The discontinuation rates due to adverse events (AEs) were 13.0 % in the slow-titration group, 31.8% in the medium-titration group and 43.5 % in the fast-titration group. Overall, the most common AEs leading to discontinuation were somnolence, speech disorder, ataxia, dizziness, and asthenia. Significantly more patients discontinued due to AEs in the fast-titration group compared with the slow-titration group (p = 0.024; odds ratio = 5.1). The incidence of patients discontinuing due to AEs in the medium-titration group was not significantly different from the slow-titration group (p = 0.124; odds ratio = 3.1). There were no clinically significant changes in ECGs or laboratory parameters at any of the titration rates. The titration rate of 150mg/7 days appears to be best tolerated.