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


This relative bioavailability study compared a fixed-dose combination (FDC) tablet of empagliflozin 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 formulation FDC was compared with a slow-dissolving side batch.

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 empagliflozin, AUC from 0 to 72 hours (AUC_0-72) for linagliptin, and maximum plasma concentration (C_max) for both drugs.

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 C_max after food compared with the fasted state, although overall exposure remained similar. The empagliflozin/linagliptin combinations were well tolerated.

This study shows that the FDC of empagliflozin 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.
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