Abstracts

Rationale: As part of the pediatric development program of lacosamide (LCM), a multi-national, long-term, open-label trial (SP848; NCT00938912) is ongoing with the objective of evaluating efficacy, safety and pharmacokinetic profiles of adjunctive LCM in children 1 month to =18 years old with focal epilepsy. Methods: Patients with focal epilepsy who had completed a previous trial (SP847 NCT00938431), and LCM-naﶥ patients (experiencing ?-2 focal seizures in the 4 weeks before screening despite treatment with 1?"3 AEDs) took part in this trial. Patients received oral LCM (syrup or tablet) up to 12 mg/kg/day, or 600 mg/day, whichever was lower. Flexible LCM and concomitant AED dosing, as well as addition of new concomitant AEDs if required, allowed for optimization of treatment. Safety results of the interim analysis for children with focal epilepsy in this ongoing long-term trial are presented here. Results: As of November 2015, 177 patients had enrolled in SP848 (137 LCM- naﶥ, 40 from SP847), and 85 (48.0%) were still in the trial. Patients were aged 0.7 to 18.0 years (median 10.3 years; Table 1), and 71.2% had comorbidities, most commonly nervous system disorders (41.2%). Mean time from epilepsy diagnosis was 5.9 years. Overall, 39.0% of patients had taken 1?"3 previous AEDs, 21.5% had taken 4?"6, and 27.1% had taken ?-7. At trial entry, 52.0% were taking 2 concomitant AEDs, and 31.6% were taking 3. The most commonly used AEDs during treatment were levetiracetam (46.3%), diazepam (33.9%), valproate (31.6%) and lamotrigine (28.2%). None of the patients aged < 4 years took lamotrigine; levetiracetam was the most common concomitant AED (66.7%) in this age group. At the interim analysis, 75.7% of patients had been exposed to LCM for >6 months, 58.2% for >12, 42.9% for >18, and 28.2% for >24. Median duration of LCM exposure was 406 days (range 1?"952 days), and mean modal dose was 8.5 mg/kg/day (SD 3.0). Most patients (94.9%) experienced ?-1 treatment-emergent adverse event (TEAE), most frequently nasopharyngitis (27.7%), vomiting (24.3%), pyrexia (23.7%) and dizziness (22.6%; Table 2). The most common drug-related TEAEs were dizziness (17.5%), somnolence (15.8%) and vomiting (10.7%). Overall, 19.2% of patients experienced serious TEAEs, most commonly AEs coded to convulsion. Discontinuations due to TEAEs occurred in 6.2% (11/177) of patients, mainly during the first 3 months (6/11), and in the 4 to < 12-year age group were most commonly due to convulsions or dizziness. No consistent or clinically relevant changes from baseline were observed for vital signs, ECGs or hematology, clinical chemistry and endocrinology parameters. Conclusions: Safety findings from this interim analysis are consistent with the known safety profile of LCM in adults participating in long-term, open-label extension trials, as well as common childhood ailments such as nasopharyngitis and pyrexia. No new safety concerns were identified. These results support further evaluation of LCM in the pediatric population. Funding: UCB Pharma-sponsored.