Abstracts

Rationale: Patients with epilepsy may experience problems with cognitive performance due to a variety of disease, psychosocial or treatment-related factors Antiepileptic drugs (AEDs) can affect cognitive function, with greater risk for adverse impact when used at high doses or as polytherapy. Lacosamide (LCM) is a new AED for adjunctive treatment of partial-onset seizures (POS) in adults. No specific tests of cognitive function with LCM are presently available. To preliminarily assess risk for adverse impact, the incidence of treatment-emergent adverse events (TEAEs) potentially related to cognition was compared for various doses of LCM vs. placebo. Most patients (84%) were already taking 2-3 concomitant AEDs ± additional VNS; many patients had a history of epilepsy surgery. Methods: Pooled safety data were evaluated from 3 double-blind phase II/III trials in adults with POS. MedDRA preferred terms for TEAEs potentially related to cognition were identified. In this retrospective analysis, incidence of individual TEAEs was calculated for placebo and each LCM dose group. The odds of experiencing any TEAE potentially related to cognition was compared with placebo (Cochran Mantel Haenszel test with adjustment for trial) for the total LCM group (all doses), the combined 200 and 400mg/day groups (approved doses), and separately for each LCM dose group. Demographic and baseline treatment data were also assessed. Results: 1308 patients (n=364 placebo; n=944 LCM) were included. The incidence of TEAEs potentially related to cognition for the combined LCM 200 and 400mg/day groups (the approved doses) was 6.1% (OR 1.3; 95% CI 0.7-2.3) vs. 4.7% for placebo. The incidence for all LCM dose groups (200 to 600mg/day) was 7.7% (OR 1.6; 95% CI: 0.9-2.7). The incidence of TEAEs potentially related to cognition appeared dose-related, occurring at 1.9% in the 200mg/day group (OR 0.4; 95% CI: 0.1-1.3), 8.5% in the 400mg/day group (OR 1.7; 95% CI: 1.0-3.2) and highest incidence (13.8%) in the unapproved 600mg/day group (OR 2.8; 95% CI 1.3-5.7). For individual MedDRA preferred terms, the only TEAE potentially related to cognition occurring with ≥2% incidence at approved doses was cognitive disorder (0.3% placebo vs. 0.4% LCM 200mg/day and 2.1% LCM 400mg/day). Memory impairment (1.6% vs. 1.1%, and 1.5%), confusional state (0.8% vs. 0.0% and 1.5%), and disturbance in attention (0.5% vs. 0% and 1.1%) were reported at an incidence of ≥1%. No major differences in baseline demographics, number or type of concomitant AEDs were seen between these groups. Conclusions: This preliminary analysis of spontaneously reported TEAEs in LCM phase II/III clinical trials showed an overall odds for TEAEs potentially related to cognition that was not significantly different from placebo. Subgroup analyses indicated that the odds of reporting any potentially cognitive TEAE increased with dose, and was less than placebo at 200mg/day, and greatest at 600mg/day. These observations should be confirmed using formal neuropsychological testing.