Pharmacokinetics and Safety of a Fixed‐Dose Combination of Alogliptin and Extended‐Release Metformin Under Fasting and/or Fed Conditions in Healthy Adults

Abstract This phase 1, randomized, open‐label, 2 × 2 crossover study evaluated the bioequivalence of fixed‐dose combination (FDC) formulations of alogliptin (ALO) and metformin extended‐release (MET XR) compared to their individual formulations and assessed the effect of food on FDC pharmacokinetics in healthy participants. The study comprised the high‐dose bioequivalence study (ALO 25 mg/MET XR 1000 mg) and the low‐dose bioequivalence study (ALO 12.5 mg/MET XR 500 mg), both conducted under fasting conditions, and the food effect study (ALO 12.5 mg/MET XR 1000 mg) conducted under both fasting and fed conditions. Among enrolled participants, 46 of 50 completed the high‐dose bioequivalence study, 45 of 51 completed the low‐dose bioequivalence study, and 22 of 26 completed the food effect study. Plasma concentrations were analyzed using liquid chromatography‐tandem mass spectrometry. The geometric mean ratios of AUC last and C max for the FDC versus individual formulations were within the bioequivalence range (0.80‐1.25) for both ALO and MET XR. ALO's pharmacokinetics were unaffected by food, while MET XR exhibited a significant food effect, with AUC last increasing by a factor of 1.63 and T max delayed by 2 hours. Given these findings, the FDC should be administered with food, consistent with MET XR monotherapy recommendations.