Long-term efficacy, safety, and tolerability, including behavior and executive functioning, during adjunctive lacosamide treatment in pediatric patients with uncontrolled epilepsy

Objectives: To evaluate long-term efficacy, safety, and tolerability, including behavior and executive functioning, during adjunctive lacosamide (LCM) treatment in pediatric patients (>= 1 month to <18 years of age) with focal-onset or generalized seizures enrolled in 2 open-label, long-term follow-up trials. Methods: Two open-label extension trials (SP848: NCT00938912; EP0034: NCT01964560) were conducted in pediatric patients who had participated in previous trials of adjunctive LCM (SP0847/NCT00938431; SP0966/NCT01969851; EP0060/NCT02710890; SP0967/NCT02477839; SP0969/NCT01921205); SP848 also directly enrolled eligible pediatric patients who had not previously participated in a clinical trial of LCM. Outcomes included retention, efficacy, and safety/tolerability. Patient improvement was assessed with Clinician's and Caregiver's Global Impression of Change scale. Behavior and emotional function was assessed with Achenbach Child Behavior Checklist (CBCL) and executive functioning was assessed with Behavior Rating Inventory of Executive Function (R) (BRIEF). Results: The pooled dataset from both trials included 905 patients (851 in the focal-onset seizure population and 47 in the generalized seizure population). In the overall population, Kaplan-Meier-estimated 1-year retention was 80 %. From baseline to the end of the treatment period, patients in the focal-onset seizure population had a median percent reduction in focal-onset seizure frequency per 28 days of 60.4 %, 55.4 % of patients were 50 % responders, and 40.8 % of patients were 75 % responders. In patients with >= 12 months of LCM treatment, >= 12 month seizure freedom during the LCM treatment period was achieved by 29.9 % of patients in the focal-onset seizure population (median duration of first >= 12-month seizure-free interval: 641 days) and 24.4 % of patients in the generalized seizure population (median duration of first >= 12-month seizure-free interval: 665 days). Improvement during LCM treatment was reported in >75 % of patients by both physicians and caregivers. Treatment-emergent adverse events (TEAEs) were reported by 749 (82.8 %) patients, most commonly pyrexia (18.9 %), upper respiratory tract infection (18.6 %), nasopharyngitis (16.2 %), vomiting (15.7 %), and somnolence (11.8 %). The most common drug-related TEAEs were somnolence (8.5 %), dizziness (7.6 %), and vomiting (5.4 %). Behavioral and emotional function was generally stable in patients 1.5-5 years of age and slightly improved in patients >= 6 years of age, and executive functioning was stable in patients <5 years of age and generally slightly improved in patients 5-18 years of age. Conclusions: In this analysis of a large patient pool from 2 open-label trials, long-term adjunctive LCM was efficacious and generally well tolerated in children with epilepsy and focal-onset or generalized seizures. Behavior and executive functioning were generally stable without observable worsening during long-term adjunctive LCM treatment.