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Empagliflozin and metformin are oral antidiabetic drugs commonly used to treat type 2 diabetes mellitus as a combination therapy. This study aimed to compare the pharmacokinetics and safety of a newly developed fixed‐dose combination of 5‐mg empagliflozin L‐proline and 1000‐mg metformin with the reference drug. A randomized, open‐label, single‐dose, 2‐period, 2‐treatment, crossover study was conducted in healthy Korean subjects. The subjects received a single oral dose of reference drug or test drug at each period. The pharmacokinetic (PK) parameters were calculated using a noncompartmental method. The geometric mean ratios and 90% confidence intervals of the plasma maximum concentration (Cmax) and area under the concentration–time curve from time zero to the last quantifiable concentration (AUClast) were calculated. A total of 27 healthy subjects were included in the PK analysis. For empagliflozin, the geometric mean ratios (90% confidence intervals) of the test to reference drug for Cmax and AUClast were 1.03 (0.99–1.08) and 1.03 (1.00–1.06), respectively. For metformin, the corresponding values for Cmax and AUClast were 0.99 (0.92–1.06) and 1.00 (0.94–1.06), respectively. In conclusion, a fixed‐dose combination of empagliflozin L‐proline and metformin showed similar PK characteristics to the reference drug, and both drugs were safe in healthy subjects. [ABSTRACT FROM AUTHOR]

This study aimed to compare the pharmacokinetic profile of combined CKD‐395 0.5/1000 mg treatment with that of the coadministration of lobeglitazone sulfate 0.5 mg and metformin hydrochloride (HCl) extended‐release (XR) 1000 mg and assess the effect of food on the pharmacokinetics of CKD‐395 0.5/1000 mg. Two clinical trials were conducted as part of an open‐label, single‐dose, randomized, 2‐period, 2‐sequence crossover study. In study 1, a total of 26 subjects received either CKD‐395 0.5/1000 mg as a test drug or coadministration of lobeglitazone sulfate 0.5 mg and metformin HCl XR 1000 mg individually as a reference treatment under fed conditions. In study 2, a total of 16 subjects received CKD‐395 0.5/1000 mg treatment under either fasted or fed conditions. Blood samples were collected at intervals from 0 to 48 hours. In study 1, the geometric mean ratios and 90% confidence intervals of pharmacokinetic parameters for lobeglitazone and metformin were all within 80%–125% in the fed condition. In study 2, there were no high‐fat meal effects on the area under the curve extending up to the last sampling time (AUClast) of lobeglitazone, but there was a decrease in the maximum plasma concentration (Cmax) of lobeglitazone by approximately 32% in the fed condition. Although the AUClast of metformin increased by approximately 70% in the fed condition, there was no effect of food on the Cmax of metformin, which is consistent with the already‐established food effect on metformin HCl XR. No adverse drug reactions or serious adverse events were observed. This study suggests that CKD‐395 0.5/1000 mg exhibits similar exposure and absorption rates to coadministration of single agents and is well tolerated under both fasted and fed conditions. [ABSTRACT FROM AUTHOR]