Pharmacokinetics of a Lobeglitazone/Metformin Fixed‐Dose Combination Tablet (CKD‐395 0.5/1000?mg) Versus Concomitant Administration of Single Agents and the Effect of Food on the Metabolism of CKD‐395 in Healthy Male Subjects

摘要

Abstract 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 (AUC last ) of lobeglitazone, but there was a decrease in the maximum plasma concentration (C max ) of lobeglitazone by approximately 32% in the fed condition. Although the AUC last of metformin increased by approximately 70% in the fed condition, there was no effect of food on the C max 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.