Dosage Form Proportionality and Food Effect of the Final Tablet Formulation of Eslicarbazepine Acetate

Methods: This was a randomized, three-way crossover, single-centre study in 18 healthy volunteers. Subjects received a single dose of oral ESL 800 mg following a standard meal in one period, and following 10 hours of fasting in two separate periods (in the form of one 800 mg tablet [reference] or two 400 mg tablets [test]). The statistical method was based upon the 90% confidence interval (CI) of maximum observed plasma drug concentration (C_max), area under the plasma concentration time curve (AUC) from time zero to the last sampling time at which concentrations were at or above the lower limit of quantification (AUC_t) and AUC from time zero to infinity (AUC_∞) geometric means ratios (GMRs) of BIA 2-005, the enantiomeric mixture of the ESL active metabolite eslicarbazepine and its enantiomer R-licarbazepine. Bioequivalence was assumed when the 90% CI of the test/reference GMR fell within the bioequivalence acceptance interval (80.00, 125.00).

Results: Following a single dose of ESL 800 mg in the forms of two 400 mg tablets and one 800 mg tablet, the test/reference GMR (%) and 90% CI for C_max, AUC_t and AUC_∞ were 100.78% (93.91, 108.16), 100.37% (97.82, 102.99) and 100.48% (97.91, 103.13), respectively. Following administration of one 800 mg tablet in fed (test) and fasting (reference) conditions, the test/reference GMR and 90% CI for C_max, AUCt and AUC8 were 100.96% (94.08, 108.35), 96.79% (94.34, 99.32) and 96.75% (94.27, 99.29), respectively. Treatments were well tolerated.