Bioequivalence and Food Effect Assessment of 2 Rivaroxaban Formulations in Healthy Chinese Volunteers: An Open, Randomized, Single‐Dose, and 4‐Period Crossover Study

Abstract Rivaroxaban is a direct factor Xa inhibitor used for the management of thromboembolic disorders. The aim of this study was to evaluate the safety, pharmacokinetic profile, and bioequivalence of a generic and a branded rivaroxaban formulation (Xarelto) under fasted and fed conditions in healthy Chinese volunteers. An open‐label, randomized, single‐dose, 4‐period complete, and replicate crossover study in healthy Chinese volunteers was performed. A single oral dose of 20 mg of 2 rivaroxaban formulations was administered to 72 healthy volunteers, with 36 in the fasted group and 36 consuming a high‐fat diet. The evaluated pharmacokinetic parameters, including maximum rivaroxaban concentration, the area under the concentration‐time curve (AUC) from time 0 to the last measurable concentration, and AUC from time 0 to infinity, were assessed for BE. The plasma concentrations of rivaroxaban were measured by a validated liquid chromatography–tandem mass spectrometry method. The geometric mean ratios with 90% confidence intervals of the maximum rivaroxaban concentration, AUC from time 0 to the last measurable concentration, and AUC from time 0 to infinity were all within the range of 80% to 125% under fasted and fed conditions. The within‐subject variability of the test and reference products was compared, and the upper limit of the 90% confidence intervals for the test‐to‐reference ratio of the within‐subject variability was <2.5, which indicated that the rivaroxaban test and the rivaroxaban reference formulation were bioequivalent. No serious adverse events were reported during either fasted or fed conditions of the study.