Trial Outcomes & Findings for Drug Interaction Study of Saxagliptin in Combination With Dapagliflozin in Healthy Participants (NCT NCT01662999)

NCT ID: NCT01662999

Last Updated: 2015-05-08

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 42 participants
• Primary outcome timeframe: Day 1 (0 h to 60 h post dose) in each period
• Results posted on: 2015-05-08

Participant Flow

20 August 2012 to 29 November 2012. Phase 1 Clinical Pharmacology center with healthy, fasted participants.

89 participants enrolled; 42 randomized and treated with study drug. 47 not randomized for following reasons: 3 withdrew consent, 38 no longer met study criteria, 6 had other reasons. Treatment was administered on Day 1 of each period after fast of 10 hours; Washout began after single dose in the period and was for at least 6 days.

Participant milestones

Measure	A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral	A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral	B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet
Period 1 STARTED	7	7	7	7	7	7
Period 1 COMPLETED	7	7	7	7	7	7
Period 1 NOT COMPLETED	0	0	0	0	0	0
Period 2 STARTED	7	7	7	7	7	7
Period 2 COMPLETED	7	7	7	7	7	7
Period 2 NOT COMPLETED	0	0	0	0	0	0
Period 3 STARTED	7	7	7	7	7	7
Period 3 COMPLETED	7	6	7	7	7	7
Period 3 NOT COMPLETED	0	1	0	0	0	0

Reasons for withdrawal

Measure	A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral	A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin Single dose of: Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral	B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Single dose of: Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Single dose of: Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet
Period 3 Withdrawal by Subject	0	1	0	0	0	0

Baseline Characteristics

Drug Interaction Study of Saxagliptin in Combination With Dapagliflozin in Healthy Participants

Baseline characteristics by cohort

Measure	A-B-C: Saxagliptin-Dapagliflozin-(Saxagliptin+Dapagliflozin) n=7 Participants Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral.	A-C-B: Saxagliptin-(Saxagliptin+Dapagliflozin)-Dapagliflozin n=7 Participants Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	B-A-C: Dapagliflozin-Saxagliptin-(Saxagliptin+Dapagliflozin) n=7 Participants Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin n=7 Participants Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin n=7 Participants Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin n=7 Participants Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	Total n=42 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=93 Participants	7 Participants n=4 Participants	7 Participants n=27 Participants	7 Participants n=483 Participants	7 Participants n=36 Participants	7 Participants n=10 Participants	42 Participants n=115 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Continuous	36.1 years STANDARD_DEVIATION 6.47 • n=93 Participants	28.7 years STANDARD_DEVIATION 5.02 • n=4 Participants	27.7 years STANDARD_DEVIATION 6.99 • n=27 Participants	32.0 years STANDARD_DEVIATION 6.51 • n=483 Participants	34.4 years STANDARD_DEVIATION 5.74 • n=36 Participants	33.3 years STANDARD_DEVIATION 7.95 • n=10 Participants	32.0 years STANDARD_DEVIATION 6.81 • n=115 Participants
Sex: Female, Male Female	2 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	3 Participants n=483 Participants	2 Participants n=36 Participants	2 Participants n=10 Participants	13 Participants n=115 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	5 Participants n=4 Participants	5 Participants n=27 Participants	4 Participants n=483 Participants	5 Participants n=36 Participants	5 Participants n=10 Participants	29 Participants n=115 Participants
Region of Enrollment United States	7 participants n=93 Participants	7 participants n=4 Participants	7 participants n=27 Participants	7 participants n=483 Participants	7 participants n=36 Participants	7 participants n=10 Participants	42 participants n=115 Participants
Body Surface Area (m^2)	1.90 m^2 STANDARD_DEVIATION 0.187 • n=93 Participants	1.92 m^2 STANDARD_DEVIATION 0.145 • n=4 Participants	1.91 m^2 STANDARD_DEVIATION 0.208 • n=27 Participants	1.95 m^2 STANDARD_DEVIATION 0.170 • n=483 Participants	1.94 m^2 STANDARD_DEVIATION 0.166 • n=36 Participants	1.85 m^2 STANDARD_DEVIATION 0.108 • n=10 Participants	1.91 m^2 STANDARD_DEVIATION 0.160 • n=115 Participants
Body Weight (kg)	77.94 kg STANDARD_DEVIATION 12.250 • n=93 Participants	78.94 kg STANDARD_DEVIATION 8.100 • n=4 Participants	76.01 kg STANDARD_DEVIATION 14.589 • n=27 Participants	80.73 kg STANDARD_DEVIATION 11.903 • n=483 Participants	79.64 kg STANDARD_DEVIATION 11.223 • n=36 Participants	71.71 kg STANDARD_DEVIATION 6.404 • n=10 Participants	77.50 kg STANDARD_DEVIATION 10.813 • n=115 Participants

PRIMARY outcome

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

Population: Pharmacokinetic (PK) Evaluable: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B).

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.

Outcome measures

Measure	10 mg Dapagliflozin n=41 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	133 ng/mL Geometric Coefficient of Variation 23	125 ng/mL Geometric Coefficient of Variation 27	—	—	—	—

PRIMARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B).

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).

Outcome measures

Measure	10 mg Dapagliflozin n=41 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	547 ng*h/mL Geometric Coefficient of Variation 23	539 ng*h/mL Geometric Coefficient of Variation 20	—	—	—	—

PRIMARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B).

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).

Outcome measures

Measure	10 mg Dapagliflozin n=41 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	529 ng*h/mL Geometric Coefficient of Variation 23	523 ng*h/mL Geometric Coefficient of Variation 19	—	—	—	—

PRIMARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	23.6 ng/mL Geometric Coefficient of Variation 31	21.9 ng/mL Geometric Coefficient of Variation 33	—	—	—	—

PRIMARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	87.8 ng*h/mL Geometric Coefficient of Variation 23	87.0 ng*h/mL Geometric Coefficient of Variation 23	—	—	—	—

PRIMARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
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	89.0 ng*h/mL Geometric Coefficient of Variation 23	88.2 ng*h/mL Geometric Coefficient of Variation 23	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. 1 participant (ACB treatment sequence) withdrew consent after having received all 3 treatments and did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). This did not impact T-HALF.

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. Actual sampling times were used for PK calculations. Tmax was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours.

Outcome measures

Measure	10 mg Dapagliflozin n=41 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Time of Maximum Observed Plasma Concentration (Tmax) of Dapagliflozin From a Single Dose of 10 mg Dapagliflozin Versus Tmax of Dapagliflozin When Co-administered With 5 mg Saxagliptin - PK Evaluable Population	1.00 hours Interval 0.5 to 2.02	1.00 hours Interval 0.5 to 2.0	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. 1 participant (ACB treatment sequence) withdrew consent after having received all 3 treatments and did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B). This did not impact T-HALF.

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. Actual sampling times were used for PK calculations. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Half-life (T-HALF) of Dapagliflozin From a Single Dose of Dapagliflozin Versus T-Half of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population	15.9 hours Standard Deviation 7.32	13.8 hours Standard Deviation 4.81	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte. One participant in the ACB treatment sequence withdrew consent after having received all 3 treatments; this participant did not provide 36-, 48-, or 60-hour samples in Period 3 (Treatment B).

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. Actual sampling times were used for PK calculations. CLT/F was calculated as Dose/AUC(INF)and was measured in milliliters per minute (mL/min).

Outcome measures

Measure	10 mg Dapagliflozin n=41 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Plasma Apparent Clearance (CLT/F) of a Single Dose of Dapagliflozin Versus CLT/F of Dapagliflozin When Co-administered With Saxagliptin - PK Evaluable Population	305 mL/min Geometric Coefficient of Variation 24	309 mL/min Geometric Coefficient of Variation 20	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). Actual sampling times were used for PK calculations. Cmax for 5-OH Saxagliptin (the major active metabolite of Saxagliptin) was derived from plasma concentration versus time data using a validated PK analysis program ™ and was measured in ng/mL.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Cmax of 5-Hydroxy (5-OH) Saxagliptin From a Single Dose Saxagliptin Versus Cmax of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population	47.0 ng/mL Geometric Coefficient of Variation 30	49.6 ng/mL Geometric Coefficient of Variation 27	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 ng/mL). 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)and was derived from the plasma concentration versus time profile for study drug using a validated PK analysis program ™. AUC (0-T) was measured in nanograms*hours per milliliter (ng*h/mL).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
AUC(0-T) of 5-OH Saxagliptin From Single Dose Saxagliptin Versus AUC(0-T) of 5-OH From Saxagliptin Co-administered With Dapagliflozin - PK Evaluable Population	267 ng*h/mL Geometric Coefficient of Variation 22	289 ng*h/mL Geometric Coefficient of Variation 22	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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 5-OH by LC-MS/MS using a validated method (quantitation range of 0.200 ng/mL to 100.0 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).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
AUC(INF) of 5-OH Saxagliptin From a Single Dose Saxagliptin Versus AUC(INF) of 5-OH When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population	273 ng*h/mL Geometric Coefficient of Variation 22	296 ng*h/mL Geometric Coefficient of Variation 22	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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. Cmax of saxagliptin total active moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin) was derived from the plasma concentration versus time profile for the saxagliptin total active moiety. Measurement was in nano Molars (nM).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Cmax of the Saxagliptin Total Active Moiety From a Single Dose of 5 mg Saxagliptin Versus Cmax of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population	138 nM Geometric Coefficient of Variation 20	137 nM Geometric Coefficient of Variation 21	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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. AUC(INF) is area under the plasma concentration-time curve from time zero extrapolated to infinity; 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) and both were derived from the plasma concentration versus time profile using a validated PK analysis program ™. Total moiety (molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin), AUC(0-T)and AUC(INF) were measured in nano Molars*hours (nM*h).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population AUC(INF) for Saxagliptin Total Active Moiety	702 nM*h Geometric Coefficient of Variation 15	735 nM*h Geometric Coefficient of Variation 15	—	—	—	—
AUC(INF) and AUC(0-T) of the Saxagliptin Total Active Moiety From a Single Dose 5 mg Saxagliptin Versus AUC(INF) and AUC(0-T) of Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable Population AUC(0-T) for Saxagliptin Total Active Moiety	694 nM*h Geometric Coefficient of Variation 15	727 nM*h Geometric Coefficient of Variation 15	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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 and 5-OH by LC-MS/MS using a validated method. Tmax was derived from the plasma concentration versus time profile for study drug and was measured in hours (h). Saxagliptin was the drug, 5-OH saxagliptin was the metabolite, and Saxagliptin total Active Moiety was molar summations of saxagliptin exposure parameter with one-half the molar exposure parameters for 5-OH Saxagliptin.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population Tmax of Saxagliptin	0.50 h Interval 0.5 to 2.0	1.00 h Interval 0.5 to 2.0	—	—	—	—
Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population Tmax of 5-OH Saxagliptin	1.50 h Interval 1.0 to 2.0	1.50 h Interval 1.0 to 3.0	—	—	—	—
Tmax of Saxagliptin, 5-OH Saxagliptin, Saxagliptin Total Active Moiety From a Single Dose of Saxagliptin Versus Tmax of Saxagliptin, 5-OH, Saxagliptin Total Active Moiety When Saxagliptin Was Co-administered With Dapagliflozin - PK Evaluable Population Tmax of Saxagliptin Total Active Moiety	1.00 h Interval 0.5 to 2.0	1.00 h Interval 0.5 to 2.0	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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. T-HALF was derived from the plasma concentration versus time profile using a validated PK analysis program ™ and was measured in hours (h).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population T-HALF for Saxagliptin	5.86 h Standard Deviation 2.23	5.38 h Standard Deviation 2.17	—	—	—	—
Half-life (T-HALF) of Saxagliptin, and 5-OH Saxagliptin From Single Dose 5 mg Saxagliptin Versus T-HALF of Saxagliptin and 5-OH From Co-administered Saxagliptin With 10 mg Dapagliflozin - PK Evaluable Population T-HALF for 5-OH Saxagliptin	15.9 h Standard Deviation 3.06	17.0 h Standard Deviation 2.97	—	—	—	—

SECONDARY outcome

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

Population: PK Evaluable Population: All participants who received at least 1 dose of any study drug and had at least 1 valid PK parameter for at least 1 analyte.

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. Saxagliptin is the parent drug and 5-OH saxagliptin is the metabolite. The molecular weights to be used for the molar ratios were 315.42 and 331.42 for saxagliptin and 5-OH, respectively. Plasma samples were analyzed for saxagliptin and for 5-OH by LC-MS/MS using a validated method (quantitation range of 0.100 ng/mL to 50.0 ng/mL and 0.200 ng/mL to 100.0 ng/mL for saxagliptin and 5-OH, respectively).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable MR_Cmax	1.90 Molar ratio Geometric Coefficient of Variation 37	2.16 Molar ratio Geometric Coefficient of Variation 37	—	—	—	—
Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable MR_AUC(INF)	2.92 Molar ratio Geometric Coefficient of Variation 33	3.19 Molar ratio Geometric Coefficient of Variation 33	—	—	—	—
Metabolite to Parent Molar Ratios (MR) of Cmax, AUC(INF), and AUC(0-T) of 5-OH Saxagliptin and Saxagliptin From a Single Dose 5 mg Saxagliptin Versus MR of Saxagliptin and 5-OH When Saxagliptin Was Co-administered With 10 mg Dapagliflozin - PK Evaluable MR_AUC(0-T)	2.89 Molar ratio Geometric Coefficient of Variation 33	3.16 Molar ratio Geometric Coefficient of Variation 34	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to end of study (16 days)

Population: Safety Population = All participants who received at least one dose of any study drug.

Adverse event (AE)=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. Serious adverse event (SAE)=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug. Grade (Gr) 1=Mild, Gr 2=Moderate, Gr 3=Severe, Gr 4=Life-threatening or disabling, Gr 5=Death. End of study was approximately 16 days and was the time for a participant to conclude each of the 3 periods (including the 6 day washout between periods).

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population Participants with AEs	6 participants	9 participants	8 participants	—	—	—
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population Participants with treatment-related AEs	4 participants	4 participants	7 participants	—	—	—
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population Participants with SAEs	0 participants	0 participants	0 participants	—	—	—
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population Participants discontinuing due to AEs	0 participants	0 participants	0 participants	—	—	—
Number of Participants With Deaths, Serious Adverse Events, Adverse Events, or Discontinuations Due to Adverse Events - Safety Population Deaths	0 participants	0 participants	0 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 of each period

Population: Safety Population = All participants who received at least one dose of any study drug.

Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal (LLN); upper limit of normal (ULN); pretreatment(pre-RX); treatment (RX). Hemoglobin (g/L): <0.85* pre-RX; hematocrit (vol): <0.85*pre-RX; erythrocytes (*10^12 c/L): <0.85*pre-RX; platelet count (*10^9 c/L): <0.85*LLN if pre-RX>=LLN, or if Pre-Tx <LLN; leukocytes (*10^9 c/L): <0.85*LLN if pre-RX <LLN,or <0.9*LLN if LLN<=Pre-RX<=ULN; neutrophils+bands (*10^9 c/L): <0.85*Pre-RX if Pre-RX <1.5 or <1.5 if Pre-RX >=1.5; eosinophils (*10^9 c/L): if value >0.75; basophils (*10^9 c/L): if value >0.4; monocytes (*10^9c/L): if value >2; lymphocytes (*10^9 c/L): if value <0.750 or if value >7.50.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population Leukocytes Low	0 participants	0 participants	1 participants	—	—	—
Number of Participants With Marked Hematology Laboratory Abnormalities - Safety Population Neutrophils (absolute) Low	1 participants	1 participants	1 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 of each period

Population: Safety Population = All participants who received at least one dose of any study drug.

Blood pressure was taken while the participant was quietly seated for at least 5 minutes. Blood pressure was measured in millimeters of mercury (mmHg). Baseline was Day -1 in Period 1; study drug was administered on Day 1 of each crossover period.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population Systolic Blood Pressure	-6.0 mmHg Standard Deviation 7.41	-4.6 mmHg Standard Deviation 8.13	-7.2 mmHg Standard Deviation 8.35	—	—	—
Mean Change From Baseline in Systolic and Diastolic Blood Pressure - Safety Population Diastolic Blood Pressure	-2.6 mmHg Standard Deviation 4.94	-2.0 mmHg Standard Deviation 4.86	-3.3 mmHg Standard Deviation 6.23	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 in each period

Population: Safety Population = All participants who received at least one dose of any study drug.

Heart rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in beats per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Mean Change From Baseline in Heart Rate - Safety Population	-4.4 bpm Standard Deviation 7.04	-4.0 bpm Standard Deviation 9.64	-4.3 bpm Standard Deviation 10.52	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 in each period

Respiration rates were taken while the participant was sitting quietly for at least 5 minutes and were measured in breaths per minute (bpm). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Mean Change From Baseline in Respiration Rate - Safety Population	-0.4 bpm Standard Deviation 3.46	-1.2 bpm Standard Deviation 2.89	-0.9 bpm Standard Deviation 3.13	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 in each period

Population: Safety Population = All participants who received at least one dose of any study drug.

Participant had their temperature taken after quietly sitting for at least 5 minutes and it was measured as degrees of centigrade (C). Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Mean Change From Baseline in Temperature - Safety Population	-0.15 degrees of centigrade Standard Deviation 0.393	-0.23 degrees of centigrade Standard Deviation 0.383	-0.16 degrees of centigrade Standard Deviation 0.385	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 in each period

Population: Safety Population = All participants who received at least one dose of any study drug.

Fasted for 10 hours prior to samples taken. Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Lower limit of normal(LLN); upper limit of normal (ULN); pre-treatment(Pre-Rx). Alkaline phosphatase U/L:>1.25*Pre-RX if Pre-Rx >ULN or >1.25*ULN if Pre-Rx <=ULN; aspartate aminotransferase (AST) U/L: >1.25*Pre-Rx if Pre-Rx > ULN or 1.25*ULN if Pre-Rx <= ULN;alanine aminotransferase (ALT) U/L: >1.25*Pre-Rx if Pre-Rx>ULN or 1.25*ULN if Pre-Rx<=ULN;blood urea nitrogen (BUN)mmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.2*Pre-Rx if Pre-Rx >ULN; total bilirubin µmol/L: >1.1*ULN if Pre-Rx <=ULN or >1.25*Pre-Rx if Pre-Rx >ULN;direct bilirubin µmol/L: >1.1*ULN if Pre-Rx <= ULN or >1.25*Pre-Rx if Pre-Rx > ULN; creatine phosphokinase (CK) U/L: >1.5*Pre-Rx if Pre-Rx >ULN or >1.5*ULN if Pre-Rx <= ULN.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population Total Bilirubin High	1 participants	1 participants	1 participants	—	—	—
Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population Direct Bilirubin High	1 participants	1 participants	1 participants	—	—	—
Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population ALT High	1 participants	0 participants	1 participants	—	—	—
Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population BUN High	1 participants	0 participants	0 participants	—	—	—
Number of Participants With Marked Chemistry Laboratory Abnormalities - Safety Population CK High	0 participants	0 participants	1 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline to Day 1 of each period

Population: Safety Population = All participants who received at least one dose of any study drug. Urine WBC and RBC were not done for all 42 participants. Number of participants analyzed (N) for the 3 treatments for WBC/RBC urine were 4, 8, 6, in treatment A, B, C, respectively.

Baseline was Day -1 of Period 1; study drug was administered on Day 1 of each crossover period. Fasted for 10 hours prior to samples taken. LLN=lower limit of normal; ULN=upper limit of normal; pretreatment (Pre-Rx). Normals: Urine glucose qualitative: dipstick >=1 if Pre-Rx <1 or 2*Pre-Rx if Pre-Rx>=1; urine microscopic white blood cell count (WBC): >=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2;urine red blood cell count (RBC):>=2 if Pre-Rx <2 or >=4 if Pre-Rx >=2.

Outcome measures

Measure	10 mg Dapagliflozin n=42 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population Urine Glucose High (N=42, 42, 42)	0 participants	2 participants	5 participants	—	—	—
Number of Participants With Marked Urinalysis Laboratory Abnormalities - Safety Population Urine WBC and RBC High (N= 4, 8, 6)	0 participants	0 participants	1 participants	—	—	—

SECONDARY outcome

Timeframe: Baseline to end of study (16 days)

Population: Safety Population = All participants who received at least one dose of any study drug.

A 12-Lead electrocardiogram (ECG) was performed and recorded after the participant had been supine for at least 5 minutes. ECGs done at baseline (Day-1 of Period 1) and at end of study; therefore the results are presented by sequence, and cannot be presented by treatment. QT interval (measure between Q wave and T wave in the heart's electrical cycle); and QT interval corrected for heart rate using Fridericia's formula (QTcF) were measured in milliseconds (msec). Abnormality criteria: QT/QTcF QT or QTcF >450 msec and <=480 msec at any postdose time point and not present at baseline. QT or QTcF >480 msec and <=500 msec at any postdose time point and not present at baseline QT or QTcF >500 msec at any postdose time point and not present at baseline. QT/QTcF Increase from baseline >60 msec for at least 1 postdose measurement. Increase from baseline in QT or QTcF >30 msec for at least 1 postdose measurement, but <=60 msec for all postdose measurements.

Outcome measures

Measure	10 mg Dapagliflozin n=7 Participants Treatment B: Single dose oral tablet of 10 mg Dapagliflozin	5 mg Saxagliptin + 10 mg Dapagliflozin n=7 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg Dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=7 Participants Treatment C: Co-administration of a single dose oral tablet of 10 mg dapagliflozin plus a single dose of oral tablet of 5mg saxagliptin..	B-C-A: Dapagliflozin-(Saxagliptin+Dapagliflozin)-Saxagliptin n=7 Participants Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.	C-A-B: (Saxagliptin+Dapagliflozin)-Saxagliptin-Dapagliflozin n=7 Participants Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets,Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral.	C-B-A: (Saxagliptin+Dapagliflozin)-Dapagliflozin-Saxagliptin n=7 Participants Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral; Treatment B: Dapagliflozin 10mg, Tablet, Oral; Treatment A: Saxagliptin 5mg, Tablet, Oral.
Number of Participants With Change From Baseline in ECG Interval - Safety Population QT change from baseline >60 msec	0 participants	0 participants	0 participants	1 participants	0 participants	0 participants
Number of Participants With Change From Baseline in ECG Interval - Safety Population QT change from baseline >30 msec; <=60 msec	0 participants	4 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change From Baseline in ECG Interval - Safety Population QTcF change from baseline >60 msec	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants
Number of Participants With Change From Baseline in ECG Interval - Safety Population QTcF change from baseline >30 msec; <=60 msec	0 participants	0 participants	0 participants	0 participants	0 participants	0 participants

Adverse Events

Treatment A: Saxagliptin 5mg

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Treatment B: Dapagliflozin 10mg

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Treatment A: Saxagliptin 5mg n=42 participants at risk Saxagliptin 5mg, Tablet, Oral, Once daily, 1 day in each of 3 periods.	Treatment B: Dapagliflozin 10mg n=42 participants at risk Dapagliflozin 10mg, Tablet, Oral, Once daily, 1 day in each of 3 periods.	Treatment C: Saxagliptin 5 mg + Dapagliflozin 10 mg n=42 participants at risk Saxagliptin 5 mg + Dapagliflozin 10 mg, Tablets, Oral, Once daily, 1 day in each of 3 periods.
Nervous system disorders Headache	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	4.8% 2/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	9.5% 4/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Constipation	4.8% 2/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	4.8% 2/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Reproductive system and breast disorders Dysmenorrhea	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	4.8% 2/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Nausea	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	4.8% 2/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Abdominal distension	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Abdominal pain	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Abdominal Pain Lower	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Investigations ALT increased	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Musculoskeletal and connective tissue disorders Back pain	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Respiratory, thoracic and mediastinal disorders Cough	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
General disorders Fatigue	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Respiratory, thoracic and mediastinal disorders Nasal congestion	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
General disorders Pain	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Toothache	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.
Gastrointestinal disorders Vomiting	2.4% 1/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.	0.00% 0/42 • Day -1 to end of study (approximately 16 days). Total length of 3 crossover periods.

Additional Information

Boaz Hirschberg

AstraZeneca Pharmaceuticals

Email: ClinicalTrialTransparency@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
• Publication restrictions are in place

Restriction type: OTHER