Relative bioavailability of an empagliflozin 25-mg/linagliptin 5-mg fixed-dose combination tablet

摘要

Objective: This relative bioavailability study compared a fixed-dose combination (FDC) tablet of empaglifiozin 25 mg/linagliptin 5 mg with the corresponding individual components. In addition, the effect of food on the bioavailability of the FDC was studied, and the standard-dissolving foimulation FDC was compared with a slow-dissolving side batch. Methods: An open-label, randomized, crossover study design was used (ClinicalTrials.gov Identifier NCT01189201). Healthy volunteers (n = 42) each received three single-dose treatments: FDC standard dissolution, individual tablets, and either FDC standard dissolution with food or FDC slow dissolution. Primary endpoints for relative bioavailability comparisons were area under the plasma concentration-time curve (AUC) over time 0 to the last time point with the plasma concentration above the quantification limit (AUC(0-tz)) for empaglifiozin, AUC from 0 to 72 hours (AUC(0-72)) for linagliptin, and maximum plasma concentration (C-max) for both drugs. Results: In all three comparisons, the 90 confidence intervals for the ratios of AUCs were within the standard acceptance range (80-125) for bioequivalence. Empagliflozin and linagliptin both showed reductions in Cmax after food compared with the fasted state, although overall exposure remained similar. The empagliflozin/linagliptin combinations were well tolerated. Conclusions: This study shows that the FDC of empaglifiozin 25 mg/linagliptin 5 mg can be regarded as bioequivalent to the individual tablets. Administering the tablet after food or a tablet with a slow-dissolution profile did not have a clinically-relevant impact on the bioavailability of empagliflozin/linagliptin FDC tablets.