Abstracts

Rationale: Lacosamide (LCM) has demonstrated efficacy and safety as add-on therapy in patients receiving 1-3 concomitant AEDs. This open-label trial aimed to evaluate the efficacy and safety of LCM as first add-on for partial-onset seizures (POS) in adults. Methods: The trial (SP954; NCT00955357), comprising 6-week Titration and 24-week Maintenance Phase, and enrolled patients with ≥3 POS for 3 months before study entry, but ≤40 POS/28 days, despite appropriate treatment, into two groups: i) first add-on (patients initiating LCM as first add-on to a first monotherapy in patients with epilepsy duration ≤24 months) and ii) later add-on (patients on 1-3 concomitant AEDs, after ≥2 previous AEDs, and ≥5 years since diagnosis). LCM was initiated at 100mg/day and increased by 100mg/day per week to a target dose of 400mg/day. The primary efficacy variable was the proportion of patients who were seizure free for the first 12 weeks of the 24-week Maintenance Phase (MP1). Seizure freedom in patients receiving sodium channel blocking (SCBs) vs non-SCB (NSCBs) AEDs was also assessed. Results: 456 patients received ≥1 LCM dose (Safety Set [SS], first add-on n=96: mean age 41.0±17.1 years, median time since diagnosis 0.7 years, median baseline seizure frequency/28 days 2.8; later add-on n=360: age 38.9±12.34 years, time since diagnosis 21.2 years, baseline seizure frequency/28 days 3.7, ≥2 baseline AEDs 72.0%); 73.0% (333/456) completed MP1 (75% first add-on; 72.5% later add-on) and 69.5% (317/456) completed 24 weeks maintenance ([MP2] 70.8% first add-on; 69.2% later add-on). 19.8% of 12-week completers (66/333) were seizure-free in MP1. Among first add-on completers, 37.5% (27/72) were seizure-free in MP1, with 26.5% (18/68) seizure-free in MP1/MP2. Corresponding seizure freedom rates in the later add-on group were 14.9% (39/261) and 11.6% (29/249). 54.2% (52/96) of first add-on and 74.2% (267/360) of later add-on patients were receiving SCBs. Seizure freedom rates in MP1 were numerically higher in patients receiving concomitant NSCBs vs SCBs (first add-on: 47.2% [17/36] vs 27.8% [10/36], later add-on: 20.5% [15/73] vs 12.8% [24/188]). Improvements in Clinical Global Impression of Change (CGIC) and Patient's Global Impression of Change (PGIC) were seen in 84.9% (73/86) and 79.5% (66/83) of the first add-on group and 73.1% (253/346) and 70.9% (231/326) of the later add-on group, respectively. The most common treatment-emergent adverse events (TEAEs) in the SS were dizziness (31.3% first add-on, 33.6% later add-on), somnolence (6.3% and 15.0%) and headache (13.5% and 11.4%). The Incidence of TEAEs during the Titration Phase was higher than during the Maintenance Phase (Table). TEAEs led to discontinuation in 12.5% of first add-on patients and 19.2% of later add-on patients. Conclusions: LCM was effective in achieving seizure freedom as first and later add-on treatment for POS and the observed tolerability was consistent with the well-established tolerability profile of adjunctive LCM.