Abstracts

Rationale: The pharmacokinetic (PK) investigation of lacosamide extended-release (XR) capsules in this study aimed to shed light on the influence of food intake and sprinkle delivery on drug absorption, a critical consideration in optimizing therapeutic outcomes. While some anti-seizure medications (ASMs) have shown that food has the potential to impact oral bioavailability (BA), lacosamide immediate-release tablets have demonstrated that food does not affect the rate and extent of absorption. Lacosamide XR capsules, a novel formulation of lacosamide, was recently developed by Aucta Pharmaceuticals, Inc. This formulation allows for once-daily dosing, which may have practical clinical advantages with less fluctuations in plasma concentration at steady state.

Methods: PK parameters, safety, and tolerability of lacosamide XR capsules were investigated in an open-label, balanced, randomized, single-dose, 3-treatment condition, 3-sequence, 3-period, crossover oral BA study. Lacosamide XR 200 mg capsule (Capsule_fa) administered in the fasted (_fa) state (10-hour overnight fast), lacosamide XR 200 mg capsule (Capsule_fe) administered in the fed (_fe) state (30 minutes after the start of a high-fat high-calorie breakfast) and lacosamide XR 200 mg capsule sprinkle (Sprinkle_fa) administered in the fasted state (10-hour overnight fast, sprinkled over 15 gm of applesauce) were evaluated. SAS® software version 9.4 was used to randomize subjects (N = 18) with each subject receiving one capsule of the product in each dosing condition. Following treatment, subjects entered an 8-day washout period in which blood samples and safety profiles were collected in the first 48 hours. Plasma concentrations of lacosamide were measured using the liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) Method. The PK parameters evaluated include maximum plasma concentration (C_max), area under the plasma concentration-time curve to time t (AUC_0-t), and area under the plasma concentration-time curve extrapolated to infinity (AUC_0-∞). For lacosamide, statistical results of 90% confidence intervals (CI) for the geometric least square mean ratios for C_max, AUC_0-t, _and AUC_0-∞ were calculated. Safety and tolerability were assessed at regular intervals.

Results: 17 subjects were considered for Capsule_fa/Capsule_fe stat analysis, and 18 were considered for Capsule_fa/Sprinkle_fa stat analysis. The following tables show relevant data. One adverse event was reported. Based on safety assessments, all values and reports of all subjects were found to be within normal limits or clinically not significant.


Conclusions: The PK parameters of lacosamide XR were compared when taken in the fasted state, fed state, and when sprinkled on applesauce. Coadministration of lacosamide XR with a high-fat meal or the use of a sprinkle administration do not affect the overall exposure of lacosamide. Lacosamide XR capsules can be taken with or without meals and can be used as a sprinkle.

Funding: This study was funded by Aucta Pharmaceuticals, Inc.