Evaluation of Long-Term Treatment with Lacosamide for Partial-Onset Seizures: A Pooled Analysis of Open-Label Extension Trials (P06.125)

Abstract

Objective: To evaluate open-label treatment with lacosamide, an antiepileptic drug (AED) for the adjunctive treatment of partial-onset seizures (POS) in adults, for up to 8 years in a pooled patient population. Background Epilepsy is a chronic condition often requiring life-long treatment with AEDs; therefore, it is important to evaluate the long-term safety and efficacy of drug therapies. Design/Methods: Patients entered one of three open-label extension trials (NCT00552305; NCT00522275; NCT00515619) following completion of a corresponding phase II/III double-blind trial of adjunctive lacosamide for POS. Safety and efficacy evaluations from the three trials were pooled. Results: A total of 1,054 patients initiated open-label lacosamide treatment, representing 2997.8 patient-years exposure. The maximum treatment duration was 2,913 days. At >1, >3, and >5 years open-label treatment, 75%, 53%, and 18% of patients were exposed to lacosamide. The decrease in percentage of patients exposed after 5 years was due to premature discontinuations and study completion because of the commercial availability of lacosamide. Primary reasons for discontinuation were lack of efficacy (28%), consent withdrawal (12%), and TEAEs (11%). Common TEAEs (≥15%) were dizziness (37%), headache (19%), nasopharyngitis (16%) and diplopia (15%). TEAEs that led to discontinuation in ≥0.5% of patients were dizziness (1.7%) and convulsion (0.9%). The median percent seizure reduction from Baseline for 1-year, 3-year and 5-year completers was 52%, 60% and 65%. The ≥50% responder rate was 53%, 60% and 65% for 1-year, 3-year and 5-year completers, while the ≥75% responder rate was 26%, 31% and 41%. Of patients exposed to lacosamide for 1, 3 or 5 years, 3.0%, 2.5% and 1.6% remained seizure free. Conclusions: For patients with POS, long-term open-label treatment with lacosamide up to 8 years was generally well tolerated and associated with a reduction in seizure frequency and maintenance of efficacy. No new safety concerns were identified with long-term lacosamide treatment. Supported by: UCB Pharma. Disclosure: Dr. Rosenfeld has received personal compensation for activities with UCB, SK Life, Jazz Pharmaceuticals, and Lundbeck as an advisory board member and speaker.Dr. Rosenfeld has received research support from Pfizer, UCB Pharma, Eisai, Valeant, Medtronic, Lundbeck Pharmaceuticals, Sunovion, Artemis, SK Life, and Upsher Smith. Dr. Husain has received personal compensation for activities with UCB Pharma, Jazz Pharma, MAP Pharmaceuticals, Upsher-Smith Laboratories as a speaker.Dr. Husain has received (royalty or license fee or contractual rights) payments from book editing.Dr. Husain has received research support from UCB Pharma. Dr. Rosenow has received personal compensation for activities with UCB, EISAI, GSK, Desitin, and Medical Tribune as a speaker.Dr. Rosenow has received research support from the European Commission, the DFG (German Research Foundation) UCB, and Nihon-Koden. Dr. McShea has received personal compensation for activities with UCB Pharma as an employee. Dr. Isojarvi has received personal compensation for activities with UCB Pharma as an employee. Dr. Isojarvi holds stock and/or stock options in UCB Pharma. Dr. Doty has received personal compensation for activities with UCB Pharmaceuticals as an employee. Dr. Doty has received compensation for serving on the board of UCB Pharmaceuticals.