Abstracts

Lacosamide (LCM, SPM 927; formerly harkoseride) is a new chemical entity being developed as an oral and intravenous formulation for the treatment of partial-onset epilepsy. In a completed randomized, controlled trial (SP667), lacosamide (400 and 600mg/day) reduced seizure frequency in subjects with uncontrolled partial seizures. Lacosamide has a favorable pharmacokinetic profile with low potential for pharmacokinetic drug-drug interactions., SP755 was an international, multicenter, double-blind, placebo-controlled trial that investigated the efficacy and safety of lacosamide in subjects with uncontrolled partial seizures taking 1 to 3 concomitant antiepileptic drugs (AEDs) with or without vagus nerve stimulation. Concomitant AEDs were held stable during an 8-week baseline. Subjects (n=485) who reported at least 8 seizures with no more than a 21-day seizure-free period were randomized in a 1:1:1 ratio to placebo, lacosamide 200 or 400mg/day (given bid), respectively. Subjects were titrated over 4 weeks to the randomized dose in 100mg/week increments. Treatment was maintained for 12 weeks, followed by blinded transition to an open-label extension trial or discontinuation. Efficacy was evaluated with continuous and categorical intent-to-treat analyses of seizure frequency (maintenance vs baseline). Safety was evaluated with adverse event (AE), ECG, vital sign, and clinical laboratory data., The median percent reduction in seizure frequency was 21%, 35%, and 36% for placebo, lacosamide 200 and 400mg/day, respectively. The lacosamide 200 and 400mg/day treatment groups were statistically significant over placebo in reducing seizure frequency from Baseline to the Maintenance Phase (p = 0.0223 and 0.0325, respectively). The 50% responder rates were 26%, 35%, and 41% for placebo, lacosamide 200 and 400mg/day, respectively. Statistical analysis for responder rate over placebo was significant for lacosamide 400mg/day (p=0.0063) and approached significance for the 200mg/day group (p=0.0735).
Rates for patient discontinuations from the trial for AEs were 6%, 6%, and 16% for placebo, lacosamide 200 and 400mg/day, respectively. The most common ([ge]10% in any lacosamide group) AEs were dizziness, headache and diplopia., Data from this randomized, double-blind, placebo-controlled trial showed that adjunctive lacosamide (200 and 400mg/day) produced a statistically significant reduction in partial seizures in patients with uncontrolled partial seizures and support further development of lacosamide as an antiepileptic drug., (Supported by Schwarz Biosciences, Inc.)