Lacosamide extended-release capsules are bioequivalent to lacosamide immediate-release tablets: Pharmacokinetic observations and simulations

Objectives: Assess the bioequivalence of lacosamide extended-release (XR) capsules and immediate-release (IR) tablets and answer real-world clinical questions regarding the use of lacosamide XR. Methods: An open-label, randomized, two-treatment, two-sequence, oral comparative bioavailability study was conducted to assess the bioequivalence of two lacosamide formulations. Participants were randomized 1:1 to receive lacosamide XR capsules (400 mg once-daily) or IR tablets (200 mg twice-daily) in 1 of 2 sequences over 7day periods. Primary outcome was the area under the lacosamide concentration-time curve over 24 h at steadystate (AUC0-tau,ss). Secondary outcomes were maximum (Cmax,ss) and minimum concentrations at steady-state (Cmin,ss). Bioequivalence was established when 90% confidence intervals (CIs) for geometric least square means ratios (GLSMs) were between 80% and 125%. Adverse events (AEs) and other safety outcomes were also assessed. Pharmacokinetic simulations, including adherent and partially adherent dosing scenarios with XR and IR formulations, modeled the clinical use of lacosamide XR. Results: Thirty-five healthy adult males were enrolled in the bioequivalence study. After 7 days of study drug, mean AUC0-tau,ss, Cmax,ss, and Cmin,ss values were similar between XR and IR formulations; all 90% CIs for GLSMs were between 80% and 125%. AEs were mild and no serious AEs or other clinically significant safety findings were observed. Pharmacokinetic simulations suggested that partial adherence affected formulations similarly; and the best strategy for switching formulations was to take the morning lacosamide IR dose followed by the evening lacosamide XR dose, as this resulted in the most consistent lacosamide plasma concentrations. Conclusions: Once-daily lacosamide XR capsules were bioequivalent to twice-daily lacosamide IR tablets. Pharmacokinetic simulations indicated lacosamide XR and IR formulations were similarly affected by partial adherence, though once-daily dosing with lacosamide XR may offer clinical advantages, and formulations can be easily switched. These results support the use of lacosamide XR capsules as a once-daily alternative to lacosamide IR tablets.