Abstracts

Rationale: Retigabine (RTG; international nonproprietary name)/ezogabine (EZG; United States adopted name) is an antiepileptic drug (AED) that reduces neuronal excitability by enhancing KCNQ (K_v7) potassium channel activity. Retention rates represent a global indicator of possible reasons for medication discontinuation, including lack of efficacy and poor tolerability, and provide useful, practical information. The long-term maintenance of RTG/EZG efficacy as determined by patient retention rates was evaluated from an integrated analysis of three long-term, open-label extension studies (OLEs).Methods: Studies 212 and 303/304 (NCT00310375/NCT00310388) are long-term OLEs of double-blind, placebo-controlled trials: phase 2 Study 205 and phase 3 Studies 301/302 (NCT00232596/NCT00235755), respectively. Patients received RTG/EZG 900 mg/day in Studies 212/304 and 1050 mg/day or 1200 mg/day in Study 303 as their starting dose; thereafter, dosages of RTG/EZG (Studies 303/304, 600?1200 mg/day; Study 212, a maximum of 1200 mg/day) and background AEDs could be modified according to individual efficacy/tolerability. The probability of patient retention in the OLEs and the time to discontinuation (duration between the first dose in the OLE and the taper dose start date) were analyzed using Kaplan Meier estimates.Results: A total of 778 patients received RTG/EZG treatment in the OLEs (222 of 279 [80%] patients who completed Study 205 were treated in Study 212; 181 of 224 [81%] patients who completed Study 301 were treated in Study 303; and 375 of 409 [92%] patients who completed Study 302 were treated in Study 304). A similar proportion of patients were exposed to open-label RTG/EZG for ?12 months (51.4%, 62.4%, and 59.5% in Studies 212, 303, and 304, respectively). A similar pattern for probability of retention was observed across each of the OLEs. In the integrated analysis, probability of retention by 6 months and 12 months of open-label treatment with RTG/EZG was approximately 76% and 58%, respectively. Probability of retention at 24 months was estimated to be 41%. The median time to discontinuation was 491 days in the integrated analysis.Conclusions: Patient retention rates represent a potential indicator of long-term efficacy and tolerability. In this analysis of three OLEs, patient retention rates after 12 months of open-label adjunctive RTG/EZG were similar across each study. The probability of retention between the first and second year of open-label treatment appeared to plateau, such that a greater proportion of patients remaining on treatment beyond 12 months were retained in the study than during the first 12 months. Funded by Valeant Pharmaceuticals International and GlaxoSmithKline.