Assessing the bioequivalence of over-the-counter esomeprazole banded capsules and multiple-unit pellet system tablets .

Abstract

To demonstrate bioequivalence between two esomeprazole formulations under fasted and fed conditions. Esomeprazole 20 mg multiunit pellet system (test; MUPS) tablets and over-the-counter esomeprazole 20 mg banded capsules (reference). This open-label, randomized, 6-period crossover study assigned healthy males and females to receive single doses of each study drug under fasted or fed conditions. The primary pharmacokinetic endpoints were esomeprazole area under the concentration-time curve from time zero to infinity (AUC_inf) and maximum observed concentration (C_max). For endpoints with high within-subject standard deviations of the reference product (S_wr ≥ 0.294), a reference scaled average bioequivalence (RSAB) approach was used. For endpoints not highly variable (S_wr < 0.294), an unscaled approach was used. In the RSAB, bioequivalence was defined as the 95% criteria bound (CB) ≤ 0 and geometric mean ratios (GMRs) within 0.80, 1.25. For the unscaled approach, bioequivalence was defined as 90% confidence intervals (CIs) of the GMR being within 80%, 125%. 60 subjects were randomized, and 46 subjects (76.7%) completed all study periods. For esomeprazole AUC_inf, the variability of the reference product was low (S_wr=0.202), so the unscaled approach was used. The GMR (90% CI) was 0.948 (0.890-1.010), indicating bioequivalence. For the comparison of esomeprazole C_max, the variability of the reference product was high (S_wr = 0.304), so the RSAB approach was used. The GMR (95% CB) was 1.009 (-0.050), indicating bioequivalence. Esomeprazole 20 mg MUPS tablets and banded capsules were found to be bioequivalent based on the AUC_inf and C_max in the fasted state. .