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.

Keywords: fixed-dose combination (FDC); food effect; lobeglitazone; metformin; pharmacokinetics.