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

Study identifier:CV181-092

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 1000 mg Metformin Immediate Release (IR) Tablet Relative to 2.5 mg Saxagliptin Tablet and 1000 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

Saxagliptin, Metformin IR (glucophage), Saxagliptin + Metformin IR (FDC)

Sex

All

Actual Enrollment

Study type

Interventional

Age

19 Years - 45 Years

Date

Study Start Date: 01 Jun 2009

Primary Completion Date: 01 Jul 2009

Study Completion Date: 01 Jul 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
Other: Arm A Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions	Drug: Saxagliptin Tablet, Oral, 2.5 mg, Once Daily, 1 week Other Name: Onglyza Drug: Metformin IR (glucophage) Tablets, Oral, 1000 mg, Once Daily, 1 week Other Name: Glucophage
Other: Arm B Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions	Drug: Saxagliptin + Metformin IR (FDC) Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week Other Name: Onglyza Other Name: Glucophage
Other: Arm C Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal	Drug: Saxagliptin Tablet, Oral, 2.5 mg, Once Daily, 1 week Other Name: Onglyza Drug: Metformin IR (glucophage) Tablets, Oral, 1000 mg, Once Daily, 1 week Other Name: Glucophage
Other: Arm D Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal	Drug: Saxagliptin + Metformin IR (FDC) Tablet, Oral, Saxagliptin 2.5 mg + metformin IR 1000 mg, Once Daily, 1 Week Other Name: Onglyza Other Name: Glucophage

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
58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).

Reporting Groups

	Description
All treated participants	Participants were assigned to 1 of 4 treatment sequences (A-D-B-C, B-A-C-D, C-B-D-A, D-C-A-B). Treatment A=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fasted; Treatment B=fixed-dose combination (FDC) tablet of 2.5-mg saxagliptin/1000-mg metformin immediate release (IR), fasted; Treatment C=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fed; Treatment D=FDC tablet of 2.5-mg saxagliptin/1000-mg metformin IR, fed. The washout between each dose was at least 7 days.

Description

All treated participants

Participants were assigned to 1 of 4 treatment sequences (A-D-B-C, B-A-C-D, C-B-D-A, D-C-A-B). Treatment A=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fasted; Treatment B=fixed-dose combination (FDC) tablet of 2.5-mg saxagliptin/1000-mg metformin immediate release (IR), fasted; Treatment C=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fed; Treatment D=FDC tablet of 2.5-mg saxagliptin/1000-mg metformin IR, fed. The washout between each dose was at least 7 days.

Participant Flow: Overall Study

	All treated participants
STARTED	24
COMPLETED	18
NOT COMPLETED	6
Adverse Event	2
No Longer Met Study Criteria	1
Personal Reasons	1
Did not Return for the Clinic Visit	2

Baseline Characteristics

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

Reporting Groups

	Description
All Enrolled and Treated Participants

Baseline Measures

	All Enrolled and Treated Participants
Number of Participants [units: Participants]	24
AgeContinuous [units: years] Mean ± Standard Deviation	30 ± 6
GenderNIH [units: participants]
Female	8
Male	16
RaceEthnicityOther [units: participants]
White	20
Black	4
Body Mass Index [units: kg/m^2] Mean ± Standard Deviation	26.5 ± 3.8
weight [units: kg] Mean ± Standard Deviation	79.9 ± 15.0

Outcome Measures

1. Primary Outcome Measure: Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinite Time (AUC[INF]) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinite Time (AUC[INF])
Measure Description	Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinite Time (AUC[INF]) [units: ng*h/mL] Geometric Mean (Full Range)	47.25 (30.6 to 66.0)	48.91 (28.7 to 80.7)	52.89 (37.4 to 75.1)	51.11 (34.2 to 73.7)

Statistical Analysis 1 for Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinite Time (AUC[INF])

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	1.042
90% Confidence Interval	( 1.009 to 1.075 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve from Time Zero Extrapolated to Infinite Time (AUC[INF])

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.988
90% Confidence Interval	( 0.958 to 1.019 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

2. Primary Outcome Measure: Saxagliptin PK parameter Area under the plasma concentration-time curve from time zero to the time of the last quantifiable plasma concentration (AUC[0-T]) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Saxagliptin PK parameter Area under the plasma concentration-time curve from time zero to the time of the last quantifiable plasma concentration (AUC[0-T])
Measure Description	Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Saxagliptin PK parameter Area under the plasma concentration-time curve from time zero to the time of the last quantifiable plasma concentration (AUC[0-T]) [units: ng*h/mL] Geometric Mean (Full Range)	44.90 (29.1 to 64.3)	46.57 (27.8 to 77.7)	50.50 (35.6 to 73.2)	49.09 (33.5 to 71.3)

Statistical Analysis 1 for Saxagliptin PK parameter Area under the plasma concentration-time curve from time zero to the time of the last quantifiable plasma concentration (AUC[0-T])

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	1.045
90% Confidence Interval	( 1.013 to 1.077 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Saxagliptin PK parameter Area under the plasma concentration-time curve from time zero to the time of the last quantifiable plasma concentration (AUC[0-T])

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.992
90% Confidence Interval	( 0.962 to 1.022 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

3. Primary Outcome Measure: Saxagliptin PK Parameter Maximum observed plasma concentration (Cmax) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Saxagliptin PK Parameter Maximum observed plasma concentration (Cmax)
Measure Description	Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Saxagliptin PK Parameter Maximum observed plasma concentration (Cmax) [units: ng/mL] Geometric Mean (Full Range)	8.58 (5.2 to 15.5)	9.09 (5.5 to 17.1)	10.97 (7.6 to 18.2)	10.80 (7.4 to 15.9)

Statistical Analysis 1 for Saxagliptin PK Parameter Maximum observed plasma concentration (Cmax)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	1.077
90% Confidence Interval	( 0.978 to 1.185 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Saxagliptin PK Parameter Maximum observed plasma concentration (Cmax)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.987
90% Confidence Interval	( 0.900 to 1.083 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

4. Primary Outcome Measure: Saxagliptin PK parameter Plasma Terminal Half-life (T-HALF) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Saxagliptin PK parameter Plasma Terminal Half-life (T-HALF)
Measure Description	Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Saxagliptin PK parameter Plasma Terminal Half-life (T-HALF) [units: hours] Mean (Standard Deviation)	6.66 (1.185)	6.34 (0.941)	6.47 (1.529)	5.78 (1.333)

No statistical analysis provided for Saxagliptin PK parameter Plasma Terminal Half-life (T-HALF)

5. Primary Outcome Measure: Saxagliptin PK parameter Time of Maximum Observed Plasma Concentration (Tmax) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Saxagliptin PK parameter Time of Maximum Observed Plasma Concentration (Tmax)
Measure Description	Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Saxagliptin PK parameter Time of Maximum Observed Plasma Concentration (Tmax) [units: hours] Median (Full Range)	1.50 (0.5 to 4.0)	0.75 (0.3 to 3.0)	1.00 (0.3 to 3.0)	1.50 (0.3 to 3.0)

No statistical analysis provided for Saxagliptin PK parameter Time of Maximum Observed Plasma Concentration (Tmax)

6. Primary Outcome Measure: Metformin PK Parameter AUC(INF) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Metformin PK Parameter AUC(INF)
Measure Description	Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Metformin PK Parameter AUC(INF) [units: ng*h/mL] Geometric Mean (Full Range)	13363.46 (8872.9 to 19164.2)	12677.92 (8827.3 to 16811.6)	12357.87 (6875.3 to 15926.2)	12126.19 (7328.6 to 15424.7)

Statistical Analysis 1 for Metformin PK Parameter AUC(INF)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.974
90% Confidence Interval	( 0.921 to 1.030 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Metformin PK Parameter AUC(INF)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.966
90% Confidence Interval	( 0.915 to 1.020 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

7. Primary Outcome Measure: Metformin PK parameter AUC(0-T) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Metformin PK parameter AUC(0-T)
Measure Description	Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Metformin PK parameter AUC(0-T) [units: ng*h/mL] Geometric Mean (Full Range)	13238.43 (8782.0 to 18991.8)	12400.41 (8105.3 to 16603.8)	12124.31 (6629.2 to 15842.4)	11996.88 (7142.5 to 15326.6)

Statistical Analysis 1 for Metformin PK parameter AUC(0-T)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.962
90% Confidence Interval	( 0.906 to 1.020 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Metformin PK parameter AUC(0-T)

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.974
90% Confidence Interval	( 0.920 to 1.032 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

8. Primary Outcome Measure: Metformin PK parameter Cmax [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Metformin PK parameter Cmax
Measure Description	Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Metformin PK parameter Cmax [units: ng/mL] Geometric Mean (Full Range)	2004.99 (1187.2 to 3144.6)	1830.76 (1142.5 to 2662.5)	1666.55 (768.7 to 2256.5)	1642.90 (848.1 to 2018.3)

Statistical Analysis 1 for Metformin PK parameter Cmax

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fasted, FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.937
90% Confidence Interval	( 0.864 to 1.016 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

Statistical Analysis 2 for Metformin PK parameter Cmax

Groups^[1]	2.5-mg saxa tablet/1000-mg met tablet, fed, FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Non-Inferiority/Equivalence Test^[2]	Yes
Other^[5]	0.964
90% Confidence Interval	( 0.891 to 1.042 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	To demonstrate the bioequivalence of formulation (FDC tablet versus co-administration of separate saxagliptin tablet and metformin IR tablet) in the fasted and fed state, linear mixed model analyses were performed on log(Cmax), log[AUC(INF)] and log[AUC(0-T)] of saxagliptin and metformin, respectively. The factors in the model were sequence, period and treatment as fixed effects and subject within sequence as a random effect.
[2]	Additional details about a non-inferiority or equivalence analysis:
	Point estimates and 90% confidence intervals were calculated for the Arm B to Arm A and Arm D to Arm C ratios of geometric means for Cmax, AUC(INF) and AUC(0-T) of saxagliptin and metformin, respectively. Potency-corrected results were also provided. Bioequivalence will be concluded if the 90% confidence intervals for the test-to-reference ratios of geometric means are entirely contained within 80% to 125% for both Cmax and AUC(INF). No adjustments were made for multiplicity.
[5]	Other relevant estimation information:
	No text entered.

9. Primary Outcome Measure: Metformin PK parameter T-HALF [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Metformin PK parameter T-HALF
Measure Description	Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Metformin PK parameter T-HALF [units: hours] Mean (Standard Deviation)	8.43 (2.956)	10.58 (8.895)	11.78 (5.999)	7.63 (2.309)

No statistical analysis provided for Metformin PK parameter T-HALF

10. Primary Outcome Measure: Metformin PK parameter Tmax [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Primary
Measure Name	Metformin PK parameter Tmax
Measure Description	Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Metformin PK parameter Tmax [units: hours] Median (Full Range)	2.00 (1.0 to 4.0)	2.98 (1.5 to 4.0)	4.00 (2.0 to 4.0)	4.00 (3.0 to 4.0)

No statistical analysis provided for Metformin PK parameter Tmax

11. Secondary Outcome Measure: BMS-510849 PK parameter AUC(INF) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Secondary
Measure Name	BMS-510849 PK parameter AUC(INF)
Measure Description	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
BMS-510849 PK parameter AUC(INF) [units: ng*h/mL] Geometric Mean (Full Range)	118.54 (58.7 to 174.4)	116.19 (48.5 to 212.4)	127.67 (62.5 to 217.8)	127.25 (59.4 to 219.3)

No statistical analysis provided for BMS-510849 PK parameter AUC(INF)

12. Secondary Outcome Measure: BMS-510849 PK Parameter AUC(0-T) [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Secondary
Measure Name	BMS-510849 PK Parameter AUC(0-T)
Measure Description	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
BMS-510849 PK Parameter AUC(0-T) [units: ng*h/mL] Geometric Mean (Full Range)	108.31 (52.0 to 169.2)	106.11 (42.3 to 201.4)	117.42 (54.3 to 210.7)	117.43 (51.1 to 210.9)

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

13. Secondary Outcome Measure: BMS-510849 PK Parameter Cmax [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Secondary
Measure Name	BMS-510849 PK Parameter Cmax
Measure Description	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
BMS-510849 PK Parameter Cmax [units: ng/mL] Geometric Mean (Full Range)	16.77 (6.4 to 32.8)	15.17 (4.7 to 32.0)	18.24 (7.6 to 36.5)	18.58 (6.2 to 33.5)

No statistical analysis provided for BMS-510849 PK Parameter Cmax

14. Secondary Outcome Measure: BMS-510849 PK Parameter T-Half [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Secondary
Measure Name	BMS-510849 PK Parameter T-Half
Measure Description	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
BMS-510849 PK Parameter T-Half [units: hours] Mean (Standard Deviation)	8.05 (1.427)	7.31 (1.369)	7.48 (1.504)	7.35 (1.622)

No statistical analysis provided for BMS-510849 PK Parameter T-Half

15. Secondary Outcome Measure: BMS-510849 PK Parameter T-Max [ Time Frame: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period ]

Measure Type	Secondary
Measure Name	BMS-510849 PK Parameter T-Max
Measure Description	Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Time Frame	pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
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.
Treated participants with PK measures

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
BMS-510849 PK Parameter T-Max [units: hours] Median (Full Range)	2.00 (1.0 to 4.0)	2.00 (0.8 to 4.0)	2.00 (1.0 to 4.0)	2.00 (1.0 to 4.0)

No statistical analysis provided for BMS-510849 PK Parameter T-Max

16. Secondary Outcome Measure: Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations due to AEs [ Time Frame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject’s participation in the study. ]

Measure Type	Secondary
Measure Name	Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations due to AEs
Measure Description	An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is 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, or is an important medical event.
Time Frame	AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject’s participation in the study.
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
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations due to AEs [units: participants]
Deaths	0	0	0	0
SAEs	0	0	0	0
AEs	5	2	4	3
Discontinuations dues to AEs	0	0	1	1

No statistical analysis provided for Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations due to AEs

17. Secondary Outcome Measure: AEs of Special Interest [ Time Frame: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). ]

Measure Type	Secondary
Measure Name	AEs of Special Interest
Measure Description	See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class [SOC]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity.
Time Frame	AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days).
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
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	21	22
AEs of Special Interest [units: participants]	0	0	0	0

No statistical analysis provided for AEs of Special Interest

18. Secondary Outcome Measure: Number of Participants with Marked Laboratory Abnormalities (MA) [ Time Frame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. ]

Measure Type	Secondary
Measure Name	Number of Participants with Marked Laboratory Abnormalities (MA)
Measure Description	Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10^3 c/uL; absolute neutrophils/bands LN, 1.500x10^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L.
Time Frame	Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
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.
Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	20	21
Number of Participants with Marked Laboratory Abnormalities (MA) [units: participants]
*Leukocytes - High(>1.2 upper limit normal [ULN])**	0	0	0	1
Abs. Neutrophils/Bands-Low (<=lower LN [LLN])	1	1	1	1
*Aspartate Aminotransferase - High (>1.25 ULN)**	0	0	0	1
*Alanine Aminotransferase - High (>1.25 ULN)**	0	0	0	1
*Blood Urea Nitrogen - High (1.1 ULN)**	0	1	1	0
Creatine Kinase - High (>1.5 ULN)	1	1	0	2
Lactate Dehydrogenase - High (>1.25 ULN)	0	0	0	1

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

19. Secondary Outcome Measure: Number of Participants with Marked Urinalysis Abnormalities [ Time Frame: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4. ]

Measure Type	Secondary
Measure Name	Number of Participants with Marked Urinalysis Abnormalities
Measure Description	Protein, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Glucose, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). Blood, Urine Abnormality: if value >= 2+ (or if pretreatment value >= 1+, then >= 2 * pretreatment). White Blood Cell (WBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). Red Blood Cell (RBC), Urine Abnormality: if value >= 2+ (or if pretreatment value >= 2+, then >= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.)
Time Frame	Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.
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.
Number of Participants Analyzed=treated participants; n=number of participants evaluated for this measure (among the 6 participants who had the urinary WBC and RBC test, there are only 2 had a pre-study evaluation, and were therefore evaluable for these measures.

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	20	21
Number of Participants with Marked Urinalysis Abnormalities [units: participants]
Protein, Urine (n=19, 19, 20, 21)	0	0	0	0
Glucose, Urine (n=19, 19, 20, 21)	0	0	0	0
Blood, Urine (n=19, 19, 20, 21)	1	0	0	2
White Blood Cells, Urine (n=2, 2, 2, 2)	0	0	1	0
Red Blood Cells, Urine (n=2, 2, 2, 2)	0	0	0	0

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

20. Secondary Outcome Measure: Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities [ Time Frame: At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation ]

Measure Type	Secondary
Measure Name	Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
Measure Description	12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs.
Time Frame	At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or Discontinuation
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.
Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.

Reporting Groups

	Description
2.5-mg saxa tablet/1000-mg met tablet, fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg saxa tablet/1000-mg met tablet, fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal

Measured Values

	2.5-mg saxa tablet/1000-mg met tablet, fasted	FDC tablet 2.5-mg saxa/1000-mg met tablet, fasted	2.5-mg saxa tablet/1000-mg met tablet, fed	FDC tablet of 2.5-mg saxa/1000-mg met tablet, fed
Number of Participants Analyzed [units:participants]	19	19	20	21
Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities [units: participants]
ECG Abnormalities	0	0	0	0
Vital Sign Abnormalities	0	0	0	0
Physical Finding Abnormalities	0	0	0	0

No statistical analysis provided for Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities

Serious Adverse Events

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

Reporting Groups

	Description
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions.
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal.
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal.
Not Dosed	58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).

Serious Adverse Events

	2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted	FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted	2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed	FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed	Not Dosed
Total, serious adverse events
# participants affected / at risk	0/19 (0.00%)	0/19 (0.00%)	0/21 (0.00%)	0/24 (0.00%)	0/34 (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	5%

Reporting Groups

	Description
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions.
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed	Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal.
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed	Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal.
Not Dosed	58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).

Other Adverse Events

2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted

FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted

2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed

FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed

Not Dosed

Total, other (not including serious) adverse events

# participants affected / at risk

3/19 (15.79%)

2/19 (10.53%)

2/21 (9.52%)

3/24 (12.50%)

0/34 (0.00%)

EYE DISORDERS

EYE DISCHARGE¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

INVESTIGATIONS

ALANINE AMINOTRANSFERASE INCREASED¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

INVESTIGATIONS

ASPARTATE AMINOTRANSFERASE INCREASED¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

INVESTIGATIONS

BLOOD LACTATE DEHYDROGENASE INCREASED¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

INVESTIGATIONS

BLOOD CREATINE PHOSPHOKINASE INCREASED¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

CARDIAC DISORDERS

PALPITATIONS¹,^†

# participants affected / at risk

0/19 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

NERVOUS SYSTEM DISORDERS

HEADACHE¹,^†

# participants affected / at risk

1/19 (5.26%)

2/19 (10.53%)

2/21 (9.52%)

1/24 (4.17%)

0/34 (0.00%)

NERVOUS SYSTEM DISORDERS

DIZZINESS¹,^†

# participants affected / at risk

0/19 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

NAUSEA¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

VOMITING¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

DIARRHOEA¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

2/24 (8.33%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

DYSPEPSIA¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

FLATULENCE¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

1/24 (4.17%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

CONSTIPATION¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

GASTROINTESTINAL DISORDERS

ABDOMINAL PAIN¹,^†

# participants affected / at risk

0/19 (0.00%)

0/21 (0.00%)

1/24 (4.17%)

0/34 (0.00%)

EAR AND LABYRINTH DISORDERS

EAR PAIN¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

1/24 (4.17%)

0/34 (0.00%)

EAR AND LABYRINTH DISORDERS

EAR DISCOMFORT¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

REPRODUCTIVE SYSTEM AND BREAST DISORDERS

MENSTRUATION DELAYED¹,^†

# participants affected / at risk

0/19 (0.00%)

1/19 (5.26%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

BACK PAIN¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

PAIN IN JAW¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

COUGH¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

RHINORRHOEA¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

SINUS CONGESTION¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

0/24 (0.00%)

0/34 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

THROAT IRRITATION¹,^†

# participants affected / at risk

1/19 (5.26%)

0/19 (0.00%)

0/21 (0.00%)

0/24 (0.00%)

0/34 (0.00%)

RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS

OROPHARYNGEAL PAIN¹,^†

# participants affected / at risk

0/19 (0.00%)

1/21 (4.76%)

1/24 (4.17%)

0/34 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 12
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
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

Trial Results Summaries