Bioequivalence of China- and Germany-Manufactured Extended-Release Reduced-Mass Metformin (Glucophage® XR RM) Tablets Under Fasted and Fed Conditions in Healthy Participants: An Open-Label, Randomized, Single-Center Crossover Study

Manufactured in Germany, extended-release reduced-mass metformin (Glucophage ® XR RM; GXR-RM) tablets are a new formulation of metformin hydrochloride. A new manufacturing location has been established in China; however, the bioequivalence of GXR-RM from these two locations has not been previously reported. This study evaluated the pharmacokinetics and safety of GXR-RM 500-mg tablets manufactured in China (test product) versus Germany (reference product) in healthy Chinese adults. This open-label, randomized, two-period, two-sequence, single-center crossover trial was conducted in Beijing, China (NCT05463094; CTR20221631). Healthy Chinese adults were enrolled under fasting ( n = 58) or fed ( n = 26) conditions and randomly assigned to receive a single dose of the test or reference product. The primary endpoints were maximum observed concentration ( C max ) and area under the plasma concentration-time curve from time 0 to the last quantifiable sampling time (AUC 0– t ); bioequivalence was concluded if the 90% confidence intervals of the geometric least-squares mean test: reference ratios fell within 0.80–1.25. Under fasting conditions, the C max geometric mean [coefficient of variation (CV)] was 854 ng/mL (25.9%; test product) and 821 ng/mL (30.1%; reference product); the AUC 0– t was 5140 h·ng/mL (26.3%; test product) and 5020 h·ng/mL (29.6%; reference product); and the geometric least-squares mean ratio (90% confidence interval) of C max and AUC 0– t for the test: reference product was 1.0362 (0.9750–1.1012) and 1.0191 (0.9684–1.0725), respectively, meeting the pre-defined bioequivalence criteria. Similar results were observed under fed conditions. Both products had similar safety profiles. Our results demonstrate the bioequivalence of GXR-RM tablets manufactured in these two locations, which is important for patient adherence and regulatory approval. This trial was registered under the identifiers NCT05463094 (ClinicalTrials.gov) and CTR20221631 (Chinese Clinical Trial Register).