Abstracts

Rationale: Lacosamide (LCM) is a newer AED recently approved in the US for monotherapy in partial-onset seizures (POS) based on a historical controlled conversion to monotherapy study (SP902; NCT00520741). A 2-year open-label extension trial (SP904) assessed the long-term use and safety of LCM ≤800 mg/d as monotherapy or adjunctive therapy in patients with POS (with and without secondary generalization) who completed or exited from SP902.Methods: Patients in the SP902 trial who received LCM during the Maintenance Phase and either completed or met an exit criterion, were eligible for SP904. Investigators in SP904 could adjust the LCM dose to 150-800mg/d and add an AED to optimize tolerability and seizure reduction. If the patient exited SP902 prior to withdrawing background AEDs, he/she could enter SP904 on 1-2 concomitant AEDs, the dosages of which could be adjusted. The primary study objectives were to determine the percent of patients on LCM monotherapy at specific time points and duration of LCM monotherapy, and also to assess safety and tolerability. Safety variables were assessed in the Safety Set (patients who received ≥1 LCM dose).Results: A total of 322 patients, 16-69 years, received LCM in SP904, of whom, 210 patients (65.2%) completed and 112 (34.8%) discontinued early. The most common reason for discontinuation was consent withdrawn (9.3%). 258 patients (80.1%) had ≥1 year and 216 (67.1%) had ≥2 years’ exposure to LCM; the total subject-years of exposure was 525.5. The median daily LCM dose was 500 mg/day; 46 patients (14.3%) had a median daily LCM dose of >600 mg/day. 282 patients (87.6%) entered SP904 on LCM monotherapy. 230/282 patients received LCM for ≥12 months and 177 (77.0%) maintained LCM monotherapy for this time. 196/282 patients received LCM for ≥24 months and 126 (64.3%) maintained LCM monotherapy during this period. The median total LCM monotherapy duration was 621 days (2-791 days). 98 patients received >300-400 mg/day and had a median LCM monotherapy duration of 573.56 days; median LCM monotherapy duration in patients receiving >700 mg/day (n=11) was 727 days. 151 patients spent their entire time in SP904 on LCM monotherapy with 123 patients being on LCM monotherapy ≥12 months and 107 patients ≥24 months; median LCM monotherapy was 728 days (8-791 days). 91.0% of patients reported treatment emergent adverse events, of which the most commonly reported were dizziness (27.3%), headache (17.1%), and nausea (14.3%).Conclusions: The majority of patients entered this trial on LCM monotherapy and stayed on LCM monotherapy for periods of ≥24 months. The median daily dose was 500 mg/day. LCM monotherapy was generally well tolerated with an overall safety profile similar to its known safety profile as adjunctive treatment and consistent with that observed in the conversion to monotherapy trial, SP902. The results of this study support the use of LCM as long-term monotherapy treatment for adult patients with partial-onset seizures. UCB Pharma-sponsored