A Single-dose, Open-label, Randomized, 3 Period, 3 Treatment Crossover Study to Evaluate the Pharmacokinetics of Saxagliptin 5 mg and Dapagliflozin 10 mg When Coadministered to Fasted Healthy Subjects

Maximum Observed Plasma Concentration (Cmax) of Dapagliflozin From a Single Dose of Dapagliflozin Versus Cmax of Dapagliflozin From Co-administered Saxagliptin Plus Dapagliflozin - Pharmacokinetic Evaluable Population

时间窗: Day 1 (0 h to 60 h post dose) in each period

The geometric mean of the maximum observed plasma concentration (Cmax) is presented below; serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h,and 60 h postdose, relative to dosing on Day 1 in each cross over period and these data are summarized in the Pharmacokinetic (PK) parameter of Cmax presented here. Plasma samples were analyzed for dapagliflozin by High Performance Liquid chromatography-Mass Spectrometry (HPLC-MS/MS) using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Dapagliflozin Cmax was derived from plasma concentration versus time data using a non-compartmental method, using a validated PK analysis program ™. Actual sampling times were used for PK calculations. Cmax was reported in ng/mL.

Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration AUC(0-T) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus AUC(0-T) for Dapagliflozin When Co-administered With 5 mg Saxagliptin

时间窗: Day 1 (0h to 60h post dose) in each period

AUC(0-T) is area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method). Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(0-T) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity [AUC(INF)] of Dapagliflozin From a Single Dose of Dapagliflozin Versus AUC (INF) of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population

时间窗: Day 1 (0h to 60h post dose) in each period

AUC(INF) is area under the plasma concentration-time curve from time 0 extrapolated to infinity. Serial blood samples for determination of study drug were collected predose (0 hours (h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for dapagliflozin by HPLC-MS/MS using a validated method; nominal range of 0.200 to 100 nanograms per milliliter (ng/mL). Actual sampling times were used for PK calculations. AUC(INF) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

Maximum Observed Concentration (Cmax) of a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

时间窗: Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). Cmax for Saxagliptin was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in nanograms per milliliter (ng/mL).

AUC(0-T) of Saxagliptin From Single Dose 5 mg Saxagliptin Versus AUC(0-T) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

时间窗: Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by Liquid chromatography-Mass Spectrometry (LC-MS/MS) using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(0-T), the area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration (linear up/log down trapezoidal method) was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).

AUC(INF) of Saxagliptin From a Single Dose of 5 mg Saxagliptin Versus AUC(INF) of Saxagliptin When Co-administered With 10 mg Dapagliflozin - PK Evaluable Population

时间窗: Day 1 (0h to 60h post dose) in each period

Serial blood samples for determination of study drug were collected predose (0 h), 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h and 60 h postdose, relative to dosing on Day 1 in each cross over period. Plasma samples were analyzed for saxagliptin by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL). AUC(INF) was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in nanograms\*hours per milliliter (ng\*h/mL).