Adjunctive lacosamide for partial‐onset seizures: Efficacy and safety results from a randomized controlled trial

Summary Purpose: To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial‐onset seizures. Methods: This multicenter, double‐blind, placebo‐controlled trial randomized patients (age 16–70 years) with partial‐onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8‐week baseline, a 4‐week titration, and a 12‐week maintenance period. Results: Four hundred eighty‐five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent‐to‐treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose‐related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed. Discussion: Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial‐onset seizures in patients with epilepsy.