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.