Bioequivalence of China- and Germany-Manufactured Bisoprolol (Concor®) Tablets in Fasted and Fed Healthy Chinese Participants: A Randomized, Open-Label, Two-Way Crossover Study

Hang Yin ¹ Zhili Jin ¹ Ran Li ¹ Dandan Li ² Lusha Wang ² Ruihua Dong ^1*

• ¹ Beijing Friendship Hospital, Capital Medical University, Beijing, China
• ² Merck Serono Beijing China, Beijing, China

Background:The bioequivalence of Concor® (Merck Healthcare KGaA), a bisoprololcontaining 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 (28th February 2023-19th May 2023) compared the pharmacokinetics and safety of bisoprolol 5-mg tablets manufactured in China (test product) with bisoprolol 5-mg tablets manufactured in Germany (reference product) in healthy Chinese adults under fasted and fed conditions. Primary endpoints were Cmax, AUC0-tlast, and AUC0-∞.Result:The mean (coefficient of variation percentage) Cmax 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 Cmax 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. Geometric least squares mean ratio (90% confidence interval) for the test/reference product was 0.9565 (0.9006-1.0158) ng/mL for Cmax, 0.9761 (0.9370-1.0168) h• ng/mL for AUC0-tlast, and 0.9807 (0.9429-1.0200) h• ng/mL for AUC0-∞ (fasted condition) and 0.9966 (0.9289-1.0691) ng/mL for Cmax, 0.9672 (0.9220-1.0145) h• ng/mL for AUC0-tlast, and 0.9693 (0.9253-1.0155) h• ng/mL for AUC0-∞ (fed condition), which met the pre-defined criteria for bioequivalence. No serious treatment-emergent adverse events or deaths occurred.This study demonstrated the bioequivalence of bisoprolol 5-mg tablets manufactured in China to tablets manufactured in Germany in healthy Chinese adults.