BIOEQUIVALENCE OF RIVAROXABAN HARD CAPSULES VS. FILM-COATED TABLETS IN HEALTHY CAUCASIAN VOLUNTEERS

Rivaroxaban is an oral anticoagulant that is a selective, direct factor Xa inhibitor. It is used to prevent thrombotic events of atherosclerotic etiology and to prevent stroke and peripheral embolism in adult patients with nonvalvular atrial fibrillation. The aim of the studies was to assess the bioequivalence of two orally administered products: test (Zarixa hard capsules) vs. reference (Xarelto (R) film-coated tablets). Two crossover, two-period, randomized, open-label, laboratory-blinded studies were conducted in healthy Caucasian male and female volunteers. A single oral dose (Study 1: 10 mg fasting, Study 2: 20 mg fed) of the test or reference product was followed by a minimum seven-day washout. Blood was collected up to 48 h after administration. Plasma concentrations of rivaroxaban were measured using a validated LC-MS/MS method. The bioequivalence criteria for 90% confidence intervals (CI) of the log-transformed geometric mean ratios (test/reference) for the two primary pharmacokinetic parameters (AUC (0-t) and C max ) were set at 80.00-125.00%. Vital signs, laboratory parameters, and adverse events were monitored. A total of 34 out of 36 volunteers completed Study 1, and the geometric mean ratios were 97.96% (90% CI 93.69-102.42%) for AUC (0-t) , and 89.35% (90% CI 84.28-94.72%) for C max . All 36 volunteers completed Study 2, and the geometric mean ratios were 103.57% (90% CI 98.75-108.63%) for AUC (0-t) , and 95.17% (90% CI 87.35-103.70%) for C max . All 90% CIs for the primary pharmacokinetic parameter ratios met the acceptance criteria. There were no serious adverse events. Results of both studies indicate that the test product (Zarixa) is bioequivalent to the reference product (Xarelto (R) ). Both products were well tolerated.