Bioequivalence and safety assessment of sorafenib tosylate tablets in healthy Chinese subjects under fasting conditions

Objective This study aimed to assess the bioequivalence and safety of two formulations of sorafenib in healthy Chinese subjects under fasting conditions. Methods A single-center, randomized, open, single-dose, two-formulation, four-period, crossover study was performed in 36 healthy Chinese subjects under fasting conditions. Blood samples were collected within 120 h after administration. The plasma concentrations of sorafenib were analyzed by a validated UPLC-MS/MS method, and pharmacokinetic parameters were analyzed using a non-compartmental method. Safety was assessed on the basis of the occurrence of adverse events and laboratory findings throughout the study period. Results The GMR point estimators of C max , AUC 0-t , and AUC 0- ∞ for the two formulations were 88.97%, 81.67%, and 83.66%, respectively, which were within the bioequivalence criterion range of 80%–125%. The upper limits of the one-sided 95% confidence intervals of C max , AUC 0-t , and AUC 0- ∞ after logarithmic transformation were −0.05, −0.04 and −0.03, respectively, which were less than 0. The difference in T max between these two formulations was not statistically significant according to the Wilcoxon signed-rank test (P = 0.3650 > 0.05). Therefore, the bioequivalence between the two formulations was established under fasting conditions. All adverse events were mild and transient. Conclusion The T formulation was bioequivalent and showed a similar safety profile to the R formulation Nexavar ® (Bayer AG) in healthy Chinese subjects under fasting conditions. Clinical trial registration http://www.chinadrugtrials.org.cn/index.html , Identifier CTR20233578.