Abstracts

Rationale: Lacosamide (LCM) is a new chemical entity being developed as an oral and intravenous formulation for the treatment of partial-onset seizures. In a completed randomized, controlled trial (SP667), adjunctive lacosamide (400 and 600mg/day) significantly reduced seizure frequency in subjects with uncontrolled partial seizures. The purpose of this trial (SP754) was to investigate the efficacy and safety of oral lacosamide (400 and 600mg/day) as adjunctive treatment in subjects with uncontrolled partial-onset seizures taking 1 to 3 concomitant antiepileptic drugs (AEDs).Methods: Subjects (n=405) reporting at least 8 seizures with no more than a 21-day seizure-free period during an 8-week baseline (Baseline Phase) were randomized (1:2:1) to placebo, lacosamide 400 or 600mg/day (given bid), respectively. Concomitant AEDs were held stable throughout the trial. Subjects were titrated over 6 weeks to the randomized dose in 100mg/week increments. Treatment was maintained for 12 weeks (Maintenance Phase), followed by blinded transition to an optional open-label extension trial or discontinuation. Efficacy was evaluated with continuous and categorical intent-to-treat analyses of seizure frequency data (Maintenance Phase versus Baseline Phase). The safety evaluation included analyses of adverse event (AE), vital sign, clinical laboratory, body weight and ECG data.Results: The median percent reduction in seizure frequency per 28 days was 20.8%, 37.3%, and 37.8% for placebo, lacosamide 400 and 600mg/day, respectively. Both doses of lacosamide were statistically significant over placebo in reducing seizure frequency from Baseline to the Maintenance Phase (400mg/day: p=0.0078; 600mg/day: p=0.0061). The 50% responder rates were 18.3%, 38.3%, and 41.2% for placebo, lacosamide 400 and 600mg/day, respectively. Both doses of lacosamide were statistically significant over placebo for the responder rate analysis (400mg/day: p=0.0004; 600mg/day: p=0.0005). The most common (≥10% in any lacosamide group) AEs included dizziness, nausea, diplopia, vision blurred, vomiting, headache, tremor, coordination abnormal, somnolence, and nystagmus. Lacosamide had no clinically relevant influence on vital sign, clinical laboratory, body weight and ECG variables. On the ECG, there was a small dose-related increase in mean PR interval (4.4ms for the lacosamide 400mg/day group); however, the frequency of first degree AV block was similar in the placebo (2%) and lacosamide (2-3%) groups. Among the subjects who completed the Maintenance Phase, nine were seizure-free throughout this phase: 0 in the placebo group, 4 (2.5%) in the lacosamide 400mg/day group, and 5 (8.1%) in the lacosamide 600mg/day group.Conclusions: The results of this trial showed that oral administration of adjunctive lacosamide (400 and 600mg/day) significantly reduced seizure frequency in patients with partial-onset seizures and was generally well tolerated. (Study supported by: SCHWARZ BIOSCIENCES, Inc.)