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.

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

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