Abstracts

Lacosamide (LCM, formerly harkoseride) belongs to a novel class of functionalized amino acids with anticonvulsant activity. In vitro, LCM had a minimal interaction with the CYP-P450 system and thus was predicted to have a low potential for pharmacokinetic interaction with concomitant antiepileptic drugs (AEDs). Trial SP667 investigated the efficacy and safety of oral LCM as adjunctive therapy in subjects with uncontrolled, partial seizures taking either 2 (84%) or 1 (16%) concomitant AEDs. One important objective was to evaluate the plasma concentrations of concomitant AEDs before and during treatment with LCM. After an 8-week baseline, subjects (n=418) were randomized to placebo, 200, 400, or 600mg/day LCM (given bid). Subjects were titrated over 6 weeks to the randomized dose in 100mg/day/week increments. Treatment was maintained for 12 weeks. Concomitant AED dose regimens were to remain constant during the trial. Descriptive statistics compared end of baseline and end of maintenance plasma concentrations for the concomitant AEDs. Change from baseline at the end of maintenance for the most common AEDs in this study are shown in the table. These data show no evidence of a LCM effect on mean individual concomitant AED concentration for either the 400 or 600 mg/day dose. The 200 mg/day group results were similar.[table1]LCM (400 and 600mg) significantly reduced seizure frequency (p = 0.0023 and 0.0084, respectively). The median percent reduction in seizures was 10% (placebo), 39% (400mg) and 40% (600mg). LCM 200mg exhibited a 26% reduction in seizures (p=0.1010). Lacosamide (400 and 600mg/day) produced a statistically significant reduction in partial seizures. AED mean plasma concentrations were not affected by lacosamide, thus the observed reductions in seizure frequency were not due to increases in the plasma concentrations of concomitant AEDs. Lacosamide 200-600mg/day appears to have a minimal risk for affecting the pharmacokinetics of several commonly prescribed concomitant AEDs. (Supported by Schwarz Biosciences, Inc., RTP, NC, USA.)