OBJECTIVES:Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2). This study was undertaken to investigate the effect of food on the pharmacokinetics of 25 mg empagliflozin and to assess dose proportionality between 10 mg and 25 mg empagliflozin under fasted conditions. MATERIALS AND METHODS: In this open-label, 3-way, cross-over study, 18 healthy volunteers received 3 single doses of empagliflozin in a randomized sequence (25 mg empagliflozin under fasted conditions, 25 mg empagliflozin after a high-fat, high-calorie breakfast and 10 mg empagliflozin under fasted conditions), each separated by a washout period of at least 7 days. Serial plasma samples were collected at selected time points over a period of 72 hours. RESULTS: Administration with food had no clinically relevant effect on the area under the plasma concentration-time curve (AUC0-∞) of empagliflozin (geometric mean ratio (GMR): 84.04, 90% confidence interval (CI): 80.86 - 87.34). The decrease observed in the maximum plasma concentrations (Cmax) of empagliflozin (GMR: 63.22, 90% CI: 56.74 - 70.44) when administered with food was not considered clinically meaningful. The increases in AUC0-∞ and Cmax for 10 mg vs. 25 mg empagliflozin administered under fasting conditions were roughly dose-proportional, as demonstrated by the slope β of the regression lines being slightly less than 1 (slope β for AUC0-∞: 0.94, 95% CI: 0.90 - 0.97; slope β for Cmax: 0.91, 95% CI: 0.80 - 1.01). Empagliflozin was well tolerated under fed and fasting conditions. CONCLUSIONS: The results support administration of empagliflozin tablets independently of food. Increases in empagliflozin exposure under fasting conditions were roughly dose-proportional between 10 mg and 25 mg empagliflozin.
RCT Entities:
OBJECTIVES:Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2). This study was undertaken to investigate the effect of food on the pharmacokinetics of 25 mg empagliflozin and to assess dose proportionality between 10 mg and 25 mg empagliflozin under fasted conditions. MATERIALS AND METHODS: In this open-label, 3-way, cross-over study, 18 healthy volunteers received 3 single doses of empagliflozin in a randomized sequence (25 mg empagliflozin under fasted conditions, 25 mg empagliflozin after a high-fat, high-calorie breakfast and 10 mg empagliflozin under fasted conditions), each separated by a washout period of at least 7 days. Serial plasma samples were collected at selected time points over a period of 72 hours. RESULTS: Administration with food had no clinically relevant effect on the area under the plasma concentration-time curve (AUC0-∞) of empagliflozin (geometric mean ratio (GMR): 84.04, 90% confidence interval (CI): 80.86 - 87.34). The decrease observed in the maximum plasma concentrations (Cmax) of empagliflozin (GMR: 63.22, 90% CI: 56.74 - 70.44) when administered with food was not considered clinically meaningful. The increases in AUC0-∞ and Cmax for 10 mg vs. 25 mg empagliflozin administered under fasting conditions were roughly dose-proportional, as demonstrated by the slope β of the regression lines being slightly less than 1 (slope β for AUC0-∞: 0.94, 95% CI: 0.90 - 0.97; slope β for Cmax: 0.91, 95% CI: 0.80 - 1.01). Empagliflozin was well tolerated under fed and fasting conditions. CONCLUSIONS: The results support administration of empagliflozin tablets independently of food. Increases in empagliflozin exposure under fasting conditions were roughly dose-proportional between 10 mg and 25 mg empagliflozin.