日本人健康成人男性を対象としたエンパグリフロジン・リナグリプチン配合錠のバイオアベイラビリティに対する食事の影響―ランダム化，単回投与，2 群クロスオーバー試験―

Background This study investigated the effect of food on relative bioavailability of a fixed-dose combination（FDC）tablet containing 25 mg empagliflozin and 5 mg linagliptin after a meal compared to that in the fasted state in healthy Japanese male subjects. Methods This was an open-label, randomized, two-sequence, crossover design, PhaseⅠstudy（ClinicalTrials.gov Identifier: NCT02815644）. A total of 22 subjects were assigned to group A or B（11 subjects each）, and first administered FDC tablet once following an overnight fast（≥10 hours）or once 30 minutes after a standard Japanese breakfast according to the assigned treatment sequence. Blood samples for pharmacokinetics measurements were taken between 2 hours before and 72 hours after FDC tablet administration. Results All subjects completed the study. Compared with the fasted state, administration of FDC tablet in the fed state reduced the AUC0-tz of empagliflozin and linagliptin by 14％ and 18％, respectively（adjusted geometric mean［90％ CI］fed╱fasted ratio: empagliflozin, 85.99％ ［83.38％, 88.68％］; linagliptin, 82.19％［78.38％, 86.18％］）and the Cmax by 25％ and 44％, respectively（adjusted geometric mean［90％ CI］ fed╱fasted ratio: empagliflozin, 74.89％ ［66.27％, 84.64％］; linagliptin, 55.69％ ［48.22％, 64.33％］）. No adverse events were reported during the treatment period. Conclusion This study shows that food did not have a clinically relevant impact on the pharmacokinetics of FDC tablets containing 25 mg empagliflozin and 5 mg linagliptin in healthy Japanese male subjects. Therefore, the FDC tablet may be administered with or without food.