A Single-blind, Randomized, Single-dose, Two-sequence, Two-period, Crossover Study to Assess the Bioequivalence between Two Oral Tablet Formulations of Rivaroxaban 20mg in Healthy Mexican Volunteers.

Abstract

The objective of this study was to demonstrate the bioequivalence of 2 oral tablet formulations of rivaroxaban 20 mg in healthy Mexican volunteers under fed conditions. This phase I, single‐blind, single‐dose, randomized, two‐sequence, two‐period crossover study included 32 volunteers. Subjects were randomly assigned to one of two sequences: test formulation (single 20 mg dose) in the first period followed by the reference formulation (single 20 mg dose) in the second, or vice versa. Blood samples were collected predose and at predefined timepoints across a 48‐hour period after drug intake. Rivaroxaban plasma concentrations were measured using a validated high‐performance liquid chromatography‐tandem mass spectrometry method. Pharmacokinetic parameters included maximum plasma concentration (Cmax), area under the plasma concentration‐time curve from time zero to last measurable concentration and to infinity (AUC0‐t, AUC0‐∞), time to reach Cmax, and half‐life. Safety was evaluated through adverse‐event monitoring using subject interviews and recording of vital signs. The 90% confidence intervals for the test/reference geometric mean ratios of Cmax (100.4%–112.7%), AUC0‐t (96.5%–111.6%), and AUC0‐∞ (95.5%–109.5%) were within the bioequivalence acceptance range (80‐125%). Two adverse events (headaches) were recorded. Both formulations of rivaroxaban 20 mg tablets were bioequivalent and well tolerated in a healthy population of Mexican volunteers under fed conditions.