# Bioequivalence of China- and Germany-manufactured bisoprolol (Concor®) tablets in fasted and fed healthy Chinese participants: a randomized, open-label, two-way, crossover study

## TL;DR

This study shows that bisoprolol tablets made in China and Germany are equally effective and safe in healthy Chinese adults, both when taken on an empty stomach and after eating.

## Contribution

The study provides the first evidence of bioequivalence between China- and Germany-manufactured bisoprolol tablets in Chinese participants.

## Key findings

- The pharmacokinetic parameters Cmax and AUC were similar between the test and reference products under both fasted and fed conditions.
- All 90% confidence intervals for the geometric mean ratios fell within the bioequivalence criteria of 0.80–1.25.
- No serious adverse events were observed, indicating similar safety profiles for both products.

## Abstract

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.

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 Cmax, AUC0–tlast, and AUC0–
∞

.

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. The 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–
∞

in fasted conditions 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–
∞

in fed conditions, which met the pre-defined criteria for bioequivalence. No serious treatment-emergent adverse events or deaths were observed.

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.

identifier CTR20230391