Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (A)

Study identifier:CV181-081

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

Bioequivalence Study of the Fixed Dose Combination of 2.5 mg Saxagliptin and 500 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 500 mg Metformin IR Tablet Co-administered to Healthy Subjects in a Fasted and in a Fed State

Medical condition

Type 2 Diabetes Mellitus

Phase

Phase 1

Healthy volunteers

Yes

Study drug

Co-administration of Saxagliptin and Metformin IR, Fasted, Saxagliptin/Metformin, Fasting, Co-administration of Saxagliptin and Metformin IR, Fed, Saxagliptin/Metformin, Fed

Sex

All

Actual Enrollment

Study type

Interventional

Age

19 Years - 45 Years

Date

Study Start Date: 01 Jun 2009

Primary Completion Date: 01 Aug 2009

Study Completion Date: 01 Aug 2009

Study design

Allocation: Randomized
Endpoint Classification: Bio-equivalence Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Other

Verification:

Verified 01 May 2015 by AstraZeneca Pharmaceuticals

Collaborators

Astra-Zeneca

Inclusion and exclusion criteria

Location

Mds Pharma Services

Lincoln, NE, United States, 68502

Arms	Assigned Interventions
Experimental: S+ M, (fasted)> S/M (fed)> S/M (fasted)>S+M (fed) Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])	Drug: Co-administration of Saxagliptin and Metformin IR, Fasted Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions Other Name: Onglyza Drug: Saxagliptin/Metformin, Fasting Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions Other Name: Onglyza Other Name: Glucophage Drug: Co-administration of Saxagliptin and Metformin IR, Fed Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions Drug: Saxagliptin/Metformin, Fed Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
Experimental: S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed) Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)	Drug: Co-administration of Saxagliptin and Metformin IR, Fasted Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions Other Name: Onglyza Drug: Saxagliptin/Metformin, Fasting Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions Other Name: Onglyza Other Name: Glucophage Drug: Co-administration of Saxagliptin and Metformin IR, Fed Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions Drug: Saxagliptin/Metformin, Fed Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
Experimental: S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted) Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)	Drug: Co-administration of Saxagliptin and Metformin IR, Fasted Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions Other Name: Onglyza Drug: Saxagliptin/Metformin, Fasting Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions Other Name: Onglyza Other Name: Glucophage Drug: Co-administration of Saxagliptin and Metformin IR, Fed Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions Drug: Saxagliptin/Metformin, Fed Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
Experimental: S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted) Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)	Drug: Co-administration of Saxagliptin and Metformin IR, Fasted Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions Other Name: Onglyza Drug: Saxagliptin/Metformin, Fasting Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions Other Name: Onglyza Other Name: Glucophage Drug: Co-administration of Saxagliptin and Metformin IR, Fed Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions Drug: Saxagliptin/Metformin, Fed Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
85 participants were enrolled and 24 were treated on study. 61 participants discontinued before randomization and treatment due to: no longer meeting study criteria (n=36), withdraw of consent (n=3), study was full (n=15), participant did not call for results (n=1), completed alternate status (n=5), or did not show for check-up (n=1)

Reporting Groups

	Description
S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	Participants were randomized to receive oral co-administration of a 2.5 mg tablet of saxagliptin plus a 500 mg tablet of metformin immediate release (IR) under fasted conditions (S + M [fasted]) followed by a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions (S/M [fed]) followed by S/M under fasting conditions (S/M [fasted]) followed by S + M under fed conditions (S + M [fed])
S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	Participants were randomized to receive S/M (fasted) followed by S + M (fasted) followed by S + M (fed) followed by S/M (fed)
S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	Participants were randomized to receive S + M (fed) followed by S/M (fasted) followed by S/M (fed) followed by S+M (fasted)
S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)	Participants were randomized to receive S/M (fed) followed by S+M (fed) followed by S+M (fasted) followed by S/M (fasted)

Participant Flow for 7 periods

Period 1: First Therapy

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 2: First Washout Period

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 3: Second Therapy

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 4: Second Washout

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 5: Third Therapy

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 6: Third Washout

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Period 7: Fourth Therapy

	S+M (fasted)> S/M (fed)> S/M (fasted)>S+M (fed)	S/M (fasted)> S+M (fasted)> S+M (fed)> S/M (fed)	S+M (fed)> S/M (fasted) >S/M (fed)> S+M (fasted)	S/M (fed)> S+M (fed)> S+M (fasted)> S/M (fasted)
STARTED	6	6	6	6
COMPLETED	6	6	6	6
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
All Treated Participants	Participants were randomized to received 1 of 4 treatments 1)oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions, 2) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions, 3) oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions, or 4) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions. Participants received all 4 treatments in 1 of 4 sequences: 1-4-2-3, 2-1-3-4, 3-2-4-1, or 4-3-1-2, with a washout period between treatments of at least 1 week.

Description

All Treated Participants

Participants were randomized to received 1 of 4 treatments 1)oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions, 2) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions, 3) oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions, or 4) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions. Participants received all 4 treatments in 1 of 4 sequences: 1-4-2-3, 2-1-3-4, 3-2-4-1, or 4-3-1-2, with a washout period between treatments of at least 1 week.

Baseline Measures

	All Treated Participants
Number of Participants [units: Participants]	24
Age Continuous [units: years] Mean ± Standard Deviation	28 ± 7
Gender, Male/Female [units: participants]
Female	7
Male	17

Outcome Measures

1. Primary Outcome Measure: Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)
Measure Description	Cmax of single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax) [units: ng/mL] Mean (Standard Deviation)	8.57 (2.572)	8.61 (2.266)	11.36 (2.875)	11.51 (3.781)

Statistical Analysis 1 for Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.011
90% Confidence Interval	( 0.940 to 1.088 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate bioequivalence (BE) of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log(Cmax) of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted condition), then 20 subjects provided 97% power to conclude BE with respect to Cmax of saxagliptin. If 5% difference then 20 subjects provided 93% power to conclude BE with respect to Cmax of saxagliptin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% confidence intervals (CIs) for the test
[5]	Other relevant estimation information:
	For Cmax of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: the geometric mean of the Reference formulation in fasted state

Statistical Analysis 2 for Saxagliptin Mean Maximum Observed Plasma Concentration (Cmax)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.999
90% Confidence Interval	( 0.929 to 1.075 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log(Cmax) of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed condition), then 20 subjects provided 97% power to conclude BE with respect to Cmax of saxagliptin. If 5% difference then 20 subjects provided 93% power to conclude BE with respect to Cmax of saxagliptin.
[5]	Other relevant estimation information:
	For Cmax of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

2. Primary Outcome Measure: Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}
Measure Description	AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]} [units: ng*h/mL] Mean (Standard Deviation)	48.57 (12.864)	49.69 (12.330)	54.59 (12.407)	55.83 (12.735)

Statistical Analysis 1 for Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.029
90% Confidence Interval	( 0.993 to 1.066 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted and fed states, linear mixed model analysis was performed on log[AUC(0-T)] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted condition), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin. If 5% difference then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(0-T) of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: geometric mean of the Reference formulation in fasted state

Statistical Analysis 2 for Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Time of Last Quantifiable Concentration (AUC [0-T]}

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.021
90% Confidence Interval	( 0.986 to 1.058 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log[AUC(0-T)] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed condition), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin. If 5% difference then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(0-T) of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

3. Primary Outcome Measure: Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])
Measure Description	AUC (0-T) for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg), or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF]) [units: ng*h/mL] Mean (Standard Deviation)	50.66 (13.322)	51.74 (12.736)	56.56 (12.778)	57.86 (13.222)

Statistical Analysis 1 for Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.027
90% Confidence Interval	( 0.990 to 1.066 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log[AUC(INF)] of saxagliptin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted condition), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin. If 5% difference then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(INF) of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: geometric mean of the Reference formulation in fasted state

Statistical Analysis 2 for Saxagliptin Mean Area Under the Plasma Concentration Time Curve From Time Zero To Infinity (AUC [0-INF])

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.022
95% Confidence Interval	( 0.985 to 1.060 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log[AUC(INF)] of saxagliptin and metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of saxagliptin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed condition), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin. If 5% difference then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of saxagliptin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(INF) of saxagliptin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

4. Primary Outcome Measure: Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)
Measure Description	T-half and T-max for single-dose saxagliptin (2.5 mg), either coadministered with metformin IR (500 mg) or administered as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max) [units: hours] Mean (Standard Deviation)
T-half	5.86 (1.367)	5.55 (1.135)	5.75 (1.119)	5.72 (1.146)
T-max	1.78 (1.210)	1.23 (0.829)	1.37 (0.842)	1.42 (0.862)

No statistical analysis provided for Saxagliptin Mean Plasma Half-life (T-half) and Mean Time of Maximum Observed Plasma Concentration (T-max)

5. Primary Outcome Measure: Metformin Mean Cmax [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Metformin Mean Cmax
Measure Description	Cmax of single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Metformin Mean Cmax [units: ng/mL] Mean (Standard Deviation)	1030.22 (293.970)	1042.52 (314.365)	993.32 (198.653)	1027.70 (208.974)

Statistical Analysis 1 for Metformin Mean Cmax

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.009
90% Confidence Interval	( 0.939 to 1.084 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log(Cmax) of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted and fed), then 20 subjects provided 98% power to conclude BE with respect to Cmax of metformin. If 5% difference then 20 subjects provided 93% power to conclude BE with respect to Cmax of metformin, respectively.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For Cmax of metformin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: geometric mean of the Reference formulation in fasted fed state

Statistical Analysis 2 for Metformin Mean Cmax

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.034
90% Confidence Interval	( 0.962 to 1.111 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log(Cmax) of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed), then 20 subjects provided 98% power to conclude BE with respect to Cmax of metformin. If 5% difference then 20 subjects provided 93% power to conclude BE with respect to Cmax of metformin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For Cmax of metformin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

6. Primary Outcome Measure: Metformin Mean AUC (0-T) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Metformin Mean AUC (0-T)
Measure Description	AUC (0-T for single-dose metformin (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Metformin Mean AUC (0-T) [units: ng*h/mL] Mean (Standard Deviation)	7403.01 (1822.749)	7575.23 (1832.807)	7176.78 (1216.854)	7502.46 (1402.256)

Statistical Analysis 1 for Metformin Mean AUC (0-T)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.024
90% Confidence Interval	( 0.964 to 1.088 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log[AUC(0-T)] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of metformin. If 5% difference then 20 subjects provided 95% power to conclude BE with respect to AUC(INF) of metformin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(0-T) of metformin the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: geometric mean of the Reference formulation in fasted state

Statistical Analysis 2 for Metformin Mean AUC (0-T)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.042
90% Confidence Interval	( 0.981 to 1.108 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log[AUC(0-T)] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of metformin. If 5% difference then 20 subjects provided 95% power to conclude BE with respect to AUC(INF) of metformin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(0-T) of metformin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

7. Primary Outcome Measure: Metformin Mean AUC(0-INF) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Metformin Mean AUC(0-INF)
Measure Description	AUC (0-INF) for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg) or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Metformin Mean AUC(0-INF) [units: ng*h/mL] Mean (Standard Deviation)	7494.67 (1792.921)	7689.57 (1761.119)	7246.89 (1215.675)	7574.17 (1397.335)

Statistical Analysis 1 for Metformin Mean AUC(0-INF)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (fasted), Saxagliptin/Metformin FDC (Fasted)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.029
90% Confidence Interval	( 0.973 to 1.088 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fasted state, linear mixed model analysis was performed on log[AUC(INF)] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fasted ), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of metformin. If 5% difference then 20 subjects provided 95% power to conclude BE with respect to AUC(INF) of metformin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(INF) of metformin, the point estimate and 90% CI were calculated for the ratio of the geometric mean of the Test formulation in fasted state: the geometric mean of the Reference formulation in fasted state

Statistical Analysis 2 for Metformin Mean AUC(0-INF)

Groups^[1]	Coadministration of Saxagliptin and Metformin IR (Fed), Saxagliptin/Metformin FDC (Fed)
Non-Inferiority/Equivalence Test^[2]	Yes
Method^[3]	Mixed Models Analysis
Other^[5]	1.042
90% Confidence Interval	( 0.986 to 1.102 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate BE of FDC tablets (Test) versus co-administration of saxagliptin and metformin IR tablets (Reference) formulations in fed state, linear mixed model analysis was performed on log[AUC(INF)] of metformin. Factors in the model were sequence, period and treatment as fixed effects, and participant within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	If no difference between bioavailabilities of metformin from FDC tablet vs. co-administration of saxagliptin tablet and metformin (fed), then 20 subjects provided 99% power to conclude BE with respect to AUC(INF) of metformin. If 5% difference then 20 subjects provided 95% power to conclude BE with respect to AUC(INF) of metformin.
[3]	Other relevant information, such as adjustments or degrees of freedom:
	Bioequivalence=90% CIs for the test
[5]	Other relevant estimation information:
	For AUC(INF) of metformin, the point estimate and 90% confidence interval (CI) were calculated for the ratio of the geometric mean of the Test formulation in fed state: the geometric mean of the Reference formulation in fed state

8. Primary Outcome Measure: Metformin T-half and T-max [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Primary
Measure Name	Metformin T-half and T-max
Measure Description	T-half and T-max for single-dose metformin IR (500 mg), either coadministered with saxagliptin (2.5 mg), or administerd as FDC 2.5 mg saxagliptin/500 mg metformin IR, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Metformin T-half and T-max [units: hours] Mean (Standard Deviation)
T-Half	9.87 (5.561)	12.03 (9.014)	8.62 (3.069)	8.61 (3.288)
T-max	3.18 (0.919)	3.08 (0.762)	3.96 (0.204)	3.87 (0.680)

No statistical analysis provided for Metformin T-half and T-max

9. Secondary Outcome Measure: BMS-510849 Mean Cmax [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Secondary
Measure Name	BMS-510849 Mean Cmax
Measure Description	Cmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
BMS-510849 Mean Cmax [units: ng/mL] Mean (Standard Deviation)	16.32 (5.094)	16.10 (4.967)	18.40 (4.140)	18.72 (4.280)

No statistical analysis provided for BMS-510849 Mean Cmax

10. Secondary Outcome Measure: BMS-510849 Mean AUC (0-T) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Secondary
Measure Name	BMS-510849 Mean AUC (0-T)
Measure Description	AUC (0-T) for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administration as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
BMS-510849 Mean AUC (0-T) [units: ng*h/mL] Mean (Standard Deviation)	112.35 (20.053)	113.87 (24.141)	120.31 (22.719)	123.05 (24.821)

No statistical analysis provided for BMS-510849 Mean AUC (0-T)

11. Secondary Outcome Measure: BMS-510849 Mean AUC (0-INF) [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Secondary
Measure Name	BMS-510849 Mean AUC (0-INF)
Measure Description	AUC (0-T)= for the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administered as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
BMS-510849 Mean AUC (0-INF) [units: ng*h/mL] Mean (Standard Deviation)	120.72 (19.826)	122.74 (24.805)	129.02 (22.988)	131.88 (25.908)

No statistical analysis provided for BMS-510849 Mean AUC (0-INF)

12. Secondary Outcome Measure: BMS-510849 Mean T-half and T-max [ Time Frame: Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr ]

Measure Type	Secondary
Measure Name	BMS-510849 Mean T-half and T-max
Measure Description	T-half and Tmax of the saxagliptin metabolite BMS-510849, following single-dose saxagliptin (2.5 mg) coadministered with metformin IR (500 mg) or administerd as an FDC 2.5 mg saxagliptin/500 mg metformin IR tablet, under fasted and fed conditions.
Time Frame	Day 1: 0 hr, 0.25 hr, 0.5 hr, 0.75 hr, 1 hr, 1.5 hr, 2 hr, 3 hr, 4 hr, 6 hr, 8 hr, 12 hr, 18 hr, Day 2: 0 hr, 12 hr, Day 3: 0 hr
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
PK data set, all participants who received study drug

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
BMS-510849 Mean T-half and T-max [units: hours] Mean (Standard Deviation)
T-Half	6.53 (1.346)	6.93 (1.284)	6.73 (1.380)	6.62 (1.238)
T-max	2.40 (0.965)	2.30 (0.965)	2.35 (0.774)	2.53 (0.727)

No statistical analysis provided for BMS-510849 Mean T-half and T-max

13. Secondary Outcome Measure: Number of Participants with at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation [ Time Frame: From Day 1 through Day 45, including up to 56 days after last dose of study medication ]

Measure Type	Secondary
Measure Name	Number of Participants with at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation
Measure Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame	From Day 1 through Day 45, including up to 56 days after last dose of study medication
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Co-administration of Saxagliptin and Metformin IR (fasted)	Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin (Fasted)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Co-administration of Saxagliptin and Metformin IR (Fed)	Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions
Saxagliptin/Metformin (Fed)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
All Treated Participants	Participants were randomized to received 1 of 4 treatments 1)oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions, 2) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions, 3) oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions, or 4) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions. Participants received all 4 treatments in 1 of 4 sequences: 1-4-2-3, 2-1-3-4, 3-2-4-1, or 4-3-1-2, with a washout period between treatments of at least 1 week.

Measured Values

	Co-administration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin (Fasted)	Co-administration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin (Fed)	All Treated Participants
Number of Participants Analyzed [units:participants]	24	24	24	24	24
Number of Participants with at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation [units: participants]
Participants with at least 1 AE	6	3	4	1	7
Death	0	0	0	0	0
SAE	0	0	0	0	0
AE leading to discontinuation	0	0	0	0	0

No statistical analysis provided for Number of Participants with at Least 1 Adverse Event (AE), Death, Serious AE (SAE), or AEs Leading to Discontinuation

14. Secondary Outcome Measure: Number of Participants with Laboratory Marked Abnormalities [ Time Frame: From Day 1 through Day 45, including up to 56 days after last dose of study medication ]

Measure Type	Secondary
Measure Name	Number of Participants with Laboratory Marked Abnormalities
Measure Description	High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Leukocytes: <0.9 x LLN/ >1.2 x ULN; blood urea nitrogen (BUN): >1.1 x ULN; creatinine: >1.33 x BL; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN; creatinine kinase (CK): >1.5 x ULN; urine blood=use ≥2 x BL if value ≥2+ or BL1+
Time Frame	From Day 1 through Day 45, including up to 56 days after last dose of study medication
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Co-administration of Saxagliptin and Metformin IR (fasted)	Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin (Fasted)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Co-administration of Saxagliptin and Metformin IR (Fed)	Participants received oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions
Saxagliptin/Metformin (Fed)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions
All Treated Participants	Participants were randomized to received 1 of 4 treatments 1)oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions, 2) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions, 3) oral co-administration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fed conditions, or 4) a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions. Participants received all 4 treatments in 1 of 4 sequences: 1-4-2-3, 2-1-3-4, 3-2-4-1, or 4-3-1-2, with a washout period between treatments of at least 1 week.

Measured Values

	Co-administration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin (Fasted)	Co-administration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin (Fed)	All Treated Participants
Number of Participants Analyzed [units:participants]	24	24	24	24	24
Number of Participants with Laboratory Marked Abnormalities [units: participants]
High leukocytes	0	0	1	0	1
High BUN	0	1	0	0	1
High creatinine	0	0	1	0	1
Low phosphorus	0	1	0	0	1
High CK	0	0	1	0	1
High urine blood	0	1	0	0	1

No statistical analysis provided for Number of Participants with Laboratory Marked Abnormalities

15. Secondary Outcome Measure: Number of Participants with Clinically Relevant Electrocardiogram (ECG) Abnormalities [ Time Frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 ]

Measure Type	Secondary
Measure Name	Number of Participants with Clinically Relevant Electrocardiogram (ECG) Abnormalities
Measure Description	PR interval, QRS complex, width of QRS, QT interval, and QT corrected for heart rate adjusting for heart rate using either Bazett formula or Fridericia formula were measured. ECG abnormalities were judged to be of medical importance by the Investigator.
Time Frame	Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Number of Participants with Clinically Relevant Electrocardiogram (ECG) Abnormalities [units: participants]	0	0	0	0

No statistical analysis provided for Number of Participants with Clinically Relevant Electrocardiogram (ECG) Abnormalities

16. Secondary Outcome Measure: Number of Participants with Clinically Relevant Vital Sign Abnormalities [ Time Frame: Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3 ]

Measure Type	Secondary
Measure Name	Number of Participants with Clinically Relevant Vital Sign Abnormalities
Measure Description	Mean systolic and diastolic blood pressure, heart rate, respiration, and temperature were assessed.Vital sign abnormalities abnormalities were judged to be of medical importance by the Investigator.
Time Frame	Period 1 Day 1, Period 2 Day 1, Period 3 Day 1, Period 4 Day 1, Period 4 Day 3
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Number of Participants with Clinically Relevant Vital Sign Abnormalities [units: participants]	0	0	0	0

No statistical analysis provided for Number of Participants with Clinically Relevant Vital Sign Abnormalities

17. Secondary Outcome Measure: Number of Participant with Clinically Relevant Physical Examination Abnormalities [ Time Frame: Screen, Period 1 Day -1, prior to discharge ]

Measure Type	Secondary
Measure Name	Number of Participant with Clinically Relevant Physical Examination Abnormalities
Measure Description	A physical examination was conducted which included height and weight measurements, from which the Body Mass Index was determined. Physical examination abnormalities were judged to be of medical importance by the Investigator.
Time Frame	Screen, Period 1 Day -1, prior to discharge
Safety Issue?	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All Treated Participants

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed-dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Measured Values

	Coadministration of Saxagliptin and Metformin IR (fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Number of Participants Analyzed [units:participants]	24	24	24	24
Number of Participant with Clinically Relevant Physical Examination Abnormalities [units: participants]	0	0	0	0

No statistical analysis provided for Number of Participant with Clinically Relevant Physical Examination Abnormalities

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (Fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Serious Adverse Events

	Coadministration of Saxagliptin and Metformin IR (Fasted)	Saxagliptin/Metformin FDC (Fasted)	Coadministration of Saxagliptin and Metformin IR (Fed)	Saxagliptin/Metformin FDC (Fed)
Total, serious adverse events
# participants affected / at risk	0/24 (0.00%)	0/24 (0.00%)	0/24 (0.00%)	0/24 (0.00%)

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	4%

Reporting Groups

	Description
Coadministration of Saxagliptin and Metformin IR (Fasted)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin immediate release (IR) under fasted conditions
Saxagliptin/Metformin FDC (Fasted)	Participants received a single oral dose of a fixed dose combination (FDC) tablet of 2.5 mg saxagliptin/500 mg metformin IR under fasting conditions
Coadministration of Saxagliptin and Metformin IR (Fed)	Participants received oral coadministration of a 2.5 mg tablet of saxagliptin and a 500 mg tablet of metformin IR under fed conditions
Saxagliptin/Metformin FDC (Fed)	Participants received a single oral dose of an FDC tablet of 2.5 mg saxagliptin/500 mg metformin IR under fed conditions

Other Adverse Events

Coadministration of Saxagliptin and Metformin IR (Fasted)

Saxagliptin/Metformin FDC (Fasted)

Coadministration of Saxagliptin and Metformin IR (Fed)

Saxagliptin/Metformin FDC (Fed)

Total, other (not including serious) adverse events

# participants affected / at risk

6/24 (25.00%)

3/24 (12.50%)

4/24 (16.67%)

1/24 (4.17%)

CARDIAC DISORDERS

PALPITATIONS¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

1/24 (4.17%)

NERVOUS SYSTEM DISORDERS

DIZZINESS¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

GASTROINTESTINAL DISORDERS

NAUSEA¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN UPPER¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

GASTROINTESTINAL DISORDERS

GASTROINTESTINAL PAIN¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

EAR AND LABYRINTH DISORDERS

EAR PAIN¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

RENAL AND URINARY DISORDERS

NEPHROLITHIASIS¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

BLOOD AND LYMPHATIC SYSTEM DISORDERS

LYMPH NODE PAIN¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

SKIN AND SUBCUTANEOUS TISSUE DISORDERS

RASH¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

COUGH¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

RHINORRHOEA¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

NASAL CONGESTION¹,^†

# participants affected / at risk

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

OROPHARYNGEAL PAIN¹,^†

# participants affected / at risk

1/24 (4.17%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

INCREASED UPPER AIRWAY SECRETION¹,^†

# participants affected / at risk

1/24 (4.17%)

0/24 (0.00%)

GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS

FATIGUE¹,^†

# participants affected / at risk

2/24 (8.33%)

0/24 (0.00%)

1/24 (4.17%)

0/24 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Boaz Hirschberg
Organization:	AstraZeneca Pharmaceuticals
E-mail:	[email protected]

Documents available

BMS Clinical Trials Disclosure
Download
Investigator Inquiry form
Download
For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
Download
PhRMA link to CV181-081
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Bristol-Myers Squibb

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Mds Pharma Services

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

PhRMA link to CV181-081

Trial Results Summaries