Abstract
BACKGROUND: The bioequivalence of Concor(®) (Merck Healthcare KGaA, Darmstadt, Germany), a bisoprolol-containing tablet, manufactured in China and Concor(®) tablets manufactured in Germany has not been previously reported. METHODS: This single-center, open-label, randomized, two-period, two-sequence, crossover trial (28 February 2023-19 May 2023) compared the pharmacokinetics and safety of bisoprolol 5-mg tablets manufactured in China (test product) with those of bisoprolol 5-mg tablets manufactured in Germany (reference product) in healthy Chinese adults under fasted and fed conditions. Primary endpoints were C(max), AUC(0-tlast), and AUC(0-∞). RESULT: The mean (coefficient of variation percentage) C(max) in the fasted group was 21.2 (15.0) ng/mL (test product) and 22.1 (17.0) ng/mL (reference product). Under fed conditions, the respective C(max) values were 22.7 (18.8) ng/mL and 22.8 (15.2) ng/mL. The mean and coefficient of variation percentage for AUC were also similar between the two products. The geometric least squares mean ratio (90% confidence interval) for the test/reference product was 0.9565 (0.9006-1.0158) ng/mL for C(max), 0.9761 (0.9370-1.0168) h·ng/mL for AUC(0-tlast), and 0.9807 (0.9429-1.0200) h·ng/mL for AUC(0-∞) in fasted conditions and 0.9966 (0.9289-1.0691) ng/mL for C(max), 0.9672 (0.9220-1.0145) h·ng/mL for AUC(0-tlast), and 0.9693 (0.9253-1.0155) h·ng/mL for AUC(0-∞) in fed conditions, which met the pre-defined criteria for bioequivalence. No serious treatment-emergent adverse events or deaths were observed. CONCLUSION: This study compared the bioequivalence of bisoprolol 5-mg tablets manufactured in China to that of the tablets manufactured in Germany among healthy Chinese adults. SYSTEMATIC REVIEW REGISTRATION: identifier CTR20230391.