Objective

The purpose of this single-center, randomized, open, two-period, two-sequence crossover, single-dose administration, bioequivalence research was to evaluate the bioequivalence and safety of the generic formulations of metformin hydrochloride sustained-release (MH-SR) 500 mg tablets (test preparation [T]: Yuantang^® SR) and the original formulation (reference preparation [R]: Glucophage^® XR) in 36 healthy Chinese volunteers under postprandial conditions.

Methods

Subjects received 500 mg T/R in each period, with a 7-day washout period. Venous blood samples of 4 mL each were collected from each subject 19 times spanning predose (0 h) to 36 h postdose. The metformin concentration in deproteinized plasma was determined by high-performance liquid chromatography–tandem mass spectrometry. Bioequivalence (80.00–125.00%) was assessed by adjusted geometric mean ratios (GMRs) and two-sided 90% confidence intervals (CIs) of the area under the curve (AUC) and maximum concentration (C_max) for each component. SAS 9.4 software was used for statistical analysis and Phoenix WinNonlin software v7 was used to analyze the pharmacokinetic parameters.

Results

Thirty-four volunteers completed the clinical study. The 90% CIs (96.12–105.44% for AUC from time zero to the time of the last measurable concentration [AUC_t], 96.22–105.54% for AUC extrapolated from time zero to infinity [AUC_∞], and 98.42–105.00% for C_max) of T/R adjusted GMRs were within the bioequivalence acceptance range of 80.00–125.00%, indicating that they are bioequivalent. No serious adverse events occurred in this study, indicating that the two formulations were effective and well tolerated.

Conclusions

Yuantang^® SR was confirmed to be a well tolerated and bioequivalent alternative to Glucophage^® XR when taken under postprandial conditions in healthy Chinese volunteers. The Clinical Trials Registry Platform used for this study was http://www.chinadrugtrials.org.cn/clinicaltrials.searchlistdetail.dhtml. The trial registration numbers (TRNs) and dates of registrations were CTR20180476 (19 April 2018) for this clinical trial and CTR20171595 (11 January 2018) for the pilot trial.