Lacosamide: What Can be Expected from the Next New Antiepileptic Drug?

Abstract

Adjunctive Lacosamide for Partial-Onset Seizures: Efficacy and Safety Results from a Randomized Controlled Trial. Halasz P, Kalviainen R, Mazurkiewicz-Beldzińska M, Rosenow F, Doty P, Hebert D, Sullivan T; SP755 Study Group. Epilepsia 2009;50(3):443–453. 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.