Bioequivalence Study of Capsules versus Film Tablets Containing Rivaroxaban in Healthy Caucasian Subjects under Fasting and Fed Conditions

Abstract The bioequivalence (BE) of orally administered capsules versus film tablets containing 20 and 10 mg of rivaroxaban was assessed in 2 single‐dose, open‐label, randomized 2‐way crossover trials with a washout period of at least 1 week. The study for the 10 mg strength was conducted under fasting conditions (n = 68) and the study for the 20 mg strength under fed conditions (n = 52). Blood samples were collected over a 36‐hour period and concentrations were assayed using a liquid chromatography tandem mass spectrometry method. Pharmacokinetic (PK) evaluation was performed with the program Phoenix WinNonlin, for non‐compartmental assessment of data. After administration of 10 mg rivaroxaban under fasting conditions, mean Area Under the time ‐ concentration Curve until the last blood sampling point (AUC t ), Area Under the time ‐ concentration Curve until infinity (AUC ∞ ), and maximum plasma concentration (C max ) were comparable (972 ng/mL*h, 1048 ng/mL*h, and 111 ng/mL, respectively, for the test and 1013 ng/mL*h, 1070 ng/mL*h and 130 ng/mL, respectively, for the reference formulation). Mean AUC t , AUC ∞ , and C max were also comparable under fed conditions after administration of 20 mg rivaroxaban (2145 ng/mL*h, 2198 ng/mL*h and 275 ng/mL, respectively, for the test and 1856 ng/mL*h, 1916 ng/mL*h and 240 ng/mL, respectively, for the reference formulation). The 90% confidence intervals for all PK parameters were within the acceptance range of 80%‐125%, suggesting BE between the generic product and the innovator product in healthy Caucasian male subjects. A clinically relevant difference in the tolerability and safety of the treatments was not detected. Study results indicated that the capsule formulations were bioequivalent with the film tablet formulations.