Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin/1000 mg Metformin XR (Manufactured in Mt Vernon, IN) Relative to 5 mg of Onglyza and 2 × 500 mg Glucophage XR

This study has been completed.

Sponsor:

Information provided by:

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT01192152

First received: August 30, 2010

Last updated: April 19, 2011

Last verified: April 2011

History of Changes

Results First Received: March 9, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Bio-equivalence Study; Intervention Model: Crossover Assignment; Masking: Open Label
Condition:	Diabetes Mellitus
Interventions:	Drug: saxagliptin Drug: Glucophage XR Drug: saxagliptin + metformin XR (FDC tablet)

Participant Flow

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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
Participants underwent screening evaluations to determine eligibility within 21 days before dosing, and were admitted to the clinical facility the evening before dosing (Day –1). On Day 1 of Period 1, a total of 30 participants who met all of the inclusion and none of the exclusion criteria were randomly assigned to 1 of 2 treatment sequences.

Reporting Groups

	Description
Treatment Sequence ABC	Treatment A (period 1): 5 mg saxagliptin + 2 Glucophage XR 500 mg under fed conditions; Treatment B (period 2):Fixed dose combination (FDC) tablet (5 mg saxa + 1000 mg metformin XR), single dose, under fed conditions; Treatment C (period 3): FDC tablet (5 mg saxa + 1000 mg metformin XR), once daily for 4 days, under fed conditions. Participants underwent a 2-day washout period between Periods 1 and 2. There was no washout between Periods 2 and 3.
Treatment Sequence BA	Treatment B (period 1):Fixed dose combination (FDC) tablet (5 mg saxa + 1000 mg metformin XR), single dose, under fed conditions; Treatment A (period 2): 5 mg saxagliptin + 2 Glucophage XR 500 mg under fed conditions. Participants underwent a 2-day washout period between Periods 1 and 2.

Description

Treatment Sequence ABC

Treatment A (period 1): 5 mg saxagliptin + 2 Glucophage XR 500 mg under fed conditions; Treatment B (period 2):Fixed dose combination (FDC) tablet (5 mg saxa + 1000 mg metformin XR), single dose, under fed conditions; Treatment C (period 3): FDC tablet (5 mg saxa + 1000 mg metformin XR), once daily for 4 days, under fed conditions. Participants underwent a 2-day washout period between Periods 1 and 2. There was no washout between Periods 2 and 3.

Treatment Sequence BA

Treatment B (period 1):Fixed dose combination (FDC) tablet (5 mg saxa + 1000 mg metformin XR), single dose, under fed conditions; Treatment A (period 2): 5 mg saxagliptin + 2 Glucophage XR 500 mg under fed conditions. Participants underwent a 2-day washout period between Periods 1 and 2.

Participant Flow for 3 periods

Period 1: Period 1

	Treatment Sequence ABC	Treatment Sequence BA
STARTED	15	15
COMPLETED	15	14
NOT COMPLETED	0	1
left prematurely (while on treatment B)	0	1

Period 2: Period 2

	Treatment Sequence ABC	Treatment Sequence BA
STARTED	15	14
COMPLETED	15	14
NOT COMPLETED	0	0

Period 3: Period 3

	Treatment Sequence ABC	Treatment Sequence BA
STARTED	15	0
COMPLETED	14	0
NOT COMPLETED	1	0
family emergency	1	0

Baseline Characteristics

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Reporting Groups

	Description
All Enrolled and Treated Participants	No text entered.

Baseline Measures

	All Enrolled and Treated Participants
Number of Participants [units: participants]	30
Age [units: years] Mean ± Standard Deviation	31.6 ± 7.76
Gender [units: participants]
Female	17
Male	13
Race/Ethnicity, Customized [units: participants]
White	22
Black or African American	8
Race/Ethnicity, Customized [units: participants]
Hispanic or Latino	13
Not Hispanic or Latino	17
Height [units: cm] Mean ± Standard Deviation	166.85 ± 9.02
Weight [units: kg] Mean ± Standard Deviation	71.56 ± 9.39
Body Mass Index [units: kg/m^2] Mean ± Standard Deviation	25.69 ± 2.70

Outcome Measures

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1. Primary:

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [ Time Frame: Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ]

Measure Type	Primary
Measure Title	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
Measure Description	No text entered.
Time Frame	Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf]) [units: ng*hr/mL] Mean ± Standard Deviation	99.45 ± 18.34	105.28 ± 23.14

Statistical Analysis 1 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

Groups ^[1]	Treatment A vs. Treatment B
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of geometric least squares means ^[3]	1.045
90% Confidence Interval	( 1.025 to 1.065 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of a 5-mg saxagliptin tablet plus two 500-mg metformin XR tablets under fed conditions, then 24 subjects would have provided 99% power to conclude bioequivalence (BE) with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided 94% and 99% power to conclude BE with respect to Cmax and AUC0-inf.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	BE was concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within 0.800 to 1.250 for both Cmax and AUC0-inf of saxagliptin.
[3]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values presented in other statistical analysis entries.

Statistical Analysis 2 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

Groups ^[1]	Treatment B
Geometric Least Squares Mean (ng*hr/mL) ^[2]	103.05

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])

Groups ^[1]	Treatment A
Geometric Least Squares Mean (ng*hr/mL) ^[2]	98.61

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment A
[2]	Other relevant estimation information:
	No text entered.

2. Primary:

Saxagliptin Observed Maximum Plasma Concentration (Cmax) [ Time Frame: Periods 1 & 2: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 & 48 hrs post-dosing. Period 3: predosing on Days 2 & 3; predosing, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hrs postdosing on Day 4 ]

Measure Type	Primary
Measure Title	Saxagliptin Observed Maximum Plasma Concentration (Cmax)
Measure Description	No text entered.
Time Frame	Periods 1 & 2: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 & 48 hrs post-dosing. Period 3: predosing on Days 2 & 3; predosing, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hrs postdosing on Day 4
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Saxagliptin Observed Maximum Plasma Concentration (Cmax) [units: ng/mL] Mean ± Standard Deviation	25.28 ± 6.40	25.75 ± 6.92	25.75 ± 7.13

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

Groups ^[1]	Treatment A vs. Treatment B
Non-Inferiority/Equivalence Test ^[2]	Yes
Ratio of geometric least squares mean ^[3]	0.999
90% Confidence Interval	( 0.948 to 1.053 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of a 5-mg saxagliptin tablet plus two 500-mg metformin XR tablets under fed conditions, then 24 subjects would have provided 99% power to conclude bioequivalence (BE) with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided 94% and 99% power to conclude BE with respect to Cmax and AUC0-inf.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	BE was concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within 0.800 to 1.250 for both Cmax and AUC0-inf of saxagliptin.
[3]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.

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

Groups ^[1]	Treatment B
Geometric Least Squares Mean (ng*hr/mL) ^[2]	24.85

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Saxagliptin Observed Maximum Plasma Concentration (Cmax)

Groups ^[1]	Treatment A
Geometric Least Squares Mean (ng*hr/mL) ^[2]	24.88

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment A
[2]	Other relevant estimation information:
	No text entered.

3. Primary:

Metformin AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Primary
Measure Title	Metformin AUC(0-inf)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to end of study. 2 participants in Treatment A & 1 in Treatment B were excluded due to the inability to estimate with acceptable accuracy a terminal slope for terminal phase concentration data. Treatment C administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	27	29	0
Metformin AUC(0-inf) [units: ng*hr/mL] Mean ± Standard Deviation	10336.18 ± 3066.13	9211.29 ± 3364.24

Statistical Analysis 1 for Metformin AUC(0-inf)

Groups ^[1]	Treatment A vs. Treatment B
Non-Inferiority/Equivalence Test ^[2]	Yes
ratio of geometric least squares means ^[3]	0.894
90% Confidence Interval	( 0.833 to 0.959 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a 5-mg saxagliptin tablet plus two 500-mg metformin XR tablets under fed conditions, then 24 subjects would have provided 99% power to conclude BE with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided at least 99% power to conclude BE with respect to Cmax and AUC0-inf.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	BE was concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within 0.800 to 1.250 for both Cmax and AUC0-inf of metformin.
[3]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.

Statistical Analysis 2 for Metformin AUC(0-inf)

Groups ^[1]	Treatment B
Geometric Least Squares Mean (ng*hr/mL) ^[2]	8713.4

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares mean for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Metformin AUC(0-inf)

Groups ^[1]	Treatment A
Geometric Least Squares Mean (ng*hr/mL) ^[2]	9746.3

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares mean for Treatment A
[2]	Other relevant estimation information:
	No text entered.

4. Primary:

Metformin Cmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ]

Measure Type	Primary
Measure Title	Metformin Cmax
Measure Description	No text entered.
Time Frame	Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Metformin Cmax [units: ng/mL] Mean ± Standard Deviation	1184.07 ± 276.12	1078.67 ± 221.72	979.93 ± 267.58

Statistical Analysis 1 for Metformin Cmax

Groups ^[1]	Treatment A vs. Treatment B
Non-Inferiority/Equivalence Test ^[2]	Yes
ratio of geometric least squares means ^[3]	0.917
90% Confidence Interval	( 0.859 to 0.980 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a 5-mg saxagliptin tablet plus two 500-mg metformin XR tablets under fed conditions, then 24 subjects would have provided 99% power to conclude BE with respect to Cmax and AUC0-inf. If there was a 5% difference, then 24 subjects would have provided at least 99% power to conclude BE with respect to Cmax and AUC0-inf.
[2]	Details of power calculation, definition of non-inferiority margin, and other key parameters:
	BE was concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within 0.800 to 1.250 for both Cmax and AUC0-inf of metformin.
[3]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.

Statistical Analysis 2 for Metformin Cmax

Groups ^[1]	Treatment B
Geometric Least Squares Mean (ng*hr/mL) ^[2]	1055.9

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Metformin Cmax

Groups ^[1]	Treatment A
Geometric Least Squares Mean (ng*hr/mL) ^[2]	1151.2

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment A
[2]	Other relevant estimation information:
	No text entered.

5. Secondary:

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) [ Time Frame: Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ]

Measure Type	Secondary
Measure Title	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])
Measure Description	No text entered.
Time Frame	Periods 1 and 2: pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.
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.
All treated participants not discontinuing prior to end of study. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	0
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t]) [units: ng*hr/mL] Mean ± Standard Deviation	97.76 ± 17.96	103.34 ± 22.73

Statistical Analysis 1 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

Groups ^[1]	Treatment A vs. Treatment B
Ratio of geometric least squares means ^[2]	1.035
90% Confidence Interval	( 1.009 to 1.062 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.

Statistical Analysis 2 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

Groups ^[1]	Treatment B
Geometric Least Squares Mean (ng*hr/mL) ^[2]	101.16

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

Groups ^[1]	Treatment A
Geometric Least Squares Mean (ng*hr/mL) ^[2]	97.72

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment A
[2]	Other relevant estimation information:
	No text entered.

6. Secondary:

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau]) [ Time Frame: Period 3: pre-dosing on Days 2 and 3; pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours post-dosing on Day 4. ]

Measure Type	Secondary
Measure Title	Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])
Measure Description	Dosing interval = 24 hours.
Time Frame	Period 3: pre-dosing on Days 2 and 3; pre-dosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours post-dosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau]) [units: ng*hr/mL] Mean ± Standard Deviation			19.20 ± 20.68

No statistical analysis provided for Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])

7. Secondary:

Saxagliptin Trough (Predose) Plasma Concentration (Cmin) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Saxagliptin Trough (Predose) Plasma Concentration (Cmin)
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Saxagliptin Trough (Predose) Plasma Concentration (Cmin) [units: ng/mL] Mean ± Standard Deviation			0.28 ± 0.10

No statistical analysis provided for Saxagliptin Trough (Predose) Plasma Concentration (Cmin)

8. Secondary:

Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg)
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg) [units: ng/mL] Mean ± Standard Deviation			4.13 ± 0.86

No statistical analysis provided for Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg)

9. Secondary:

Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %)
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %) [units: percentage of fluctuation] Mean ± Standard Deviation			611.85 ± 107.36

No statistical analysis provided for Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %)

10. Secondary:

Saxagliptin Terminal Half-life (T1/2) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	Saxagliptin Terminal Half-life (T1/2)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
Saxagliptin Terminal Half-life (T1/2) [units: ng*hr/mL] Mean ± Standard Deviation	8.69 ± 3.71	8.85 ± 4.47

No statistical analysis provided for Saxagliptin Terminal Half-life (T1/2)

11. Secondary:

Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf]) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf]) [units: ratio] Mean ± Standard Deviation	0.981 ± 0.010	0.982 ± 0.008

No statistical analysis provided for Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])

12. Secondary:

Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax) [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ]

Measure Type	Secondary
Measure Title	Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax)
Measure Description	No text entered.
Time Frame	Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax) [units: hour] Mean ± Standard Deviation	1.88 ± 0.87	1.51 ± 0.64	1.35 ± 0.51

No statistical analysis provided for Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax)

13. Secondary:

5-hydroxy Saxagliptin AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin AUC(0-inf)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
5-hydroxy Saxagliptin AUC(0-inf) [units: ng*hr/mL] Mean ± Standard Deviation	298.80 ± 69.32	296.99 ± 69.35

No statistical analysis provided for 5-hydroxy Saxagliptin AUC(0-inf)

14. Secondary:

5-hydroxy Saxagliptin AUC(0-t) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin AUC(0-t)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to end of study. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	0
5-hydroxy Saxagliptin AUC(0-t) [units: ng*hr/mL] Mean ± Standard Deviation	293.06 ± 68.28	289.37 ± 68.72

No statistical analysis provided for 5-hydroxy Saxagliptin AUC(0-t)

15. Secondary:

5-hydroxy Saxagliptin AUC(0-tau) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin AUC(0-tau)
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
5-hydroxy Saxagliptin AUC(0-tau) [units: ng*hr/mL] Mean ± Standard Deviation			318.47 ± 54.95

No statistical analysis provided for 5-hydroxy Saxagliptin AUC(0-tau)

16. Secondary:

5-hydroxy Saxagliptin Cmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin Cmax
Measure Description	No text entered.
Time Frame	Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
5-hydroxy Saxagliptin Cmax [units: ng/mL] Mean ± Standard Deviation	54.69 ± 17.00	51.32 ± 16.19	59.87 ± 13.83

No statistical analysis provided for 5-hydroxy Saxagliptin Cmax

17. Secondary:

5-hydroxy Saxagliptin Cmin [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin Cmin
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
5-hydroxy Saxagliptin Cmin [units: ng/mL] Mean ± Standard Deviation			1.51 ± 0.22

No statistical analysis provided for 5-hydroxy Saxagliptin Cmin

18. Secondary:

5-hydroxy Saxagliptin Cavg [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin Cavg
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
5-hydroxy Saxagliptin Cavg [units: ng/mL] Mean ± Standard Deviation			13.27 ± 2.29

No statistical analysis provided for 5-hydroxy Saxagliptin Cavg

19. Secondary:

5-hydroxy Saxagliptin Fluctuation % [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin Fluctuation %
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
5-hydroxy Saxagliptin Fluctuation % [units: percentage of fluctuation] Mean ± Standard Deviation			437.09 ± 43.97

No statistical analysis provided for 5-hydroxy Saxagliptin Fluctuation %

20. Secondary:

5-hydroxy Saxagliptin T1/2 [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin T1/2
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours post-dosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
5-hydroxy Saxagliptin T1/2 [units: ng*hr/mL] Mean ± Standard Deviation	13.48 ± 1.78	13.82 ± 2.52

No statistical analysis provided for 5-hydroxy Saxagliptin T1/2

21. Secondary:

5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf) [units: ratio] Mean ± Standard Deviation	0.975 ± 0.009	0.973 ± 0.010

No statistical analysis provided for 5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf)

22. Secondary:

5-hydroxy Saxagliptin Tmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ]

Measure Type	Secondary
Measure Title	5-hydroxy Saxagliptin Tmax
Measure Description	No text entered.
Time Frame	Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
5-hydroxy Saxagliptin Tmax [units: hour] Mean ± Standard Deviation	2.69 ± 0.80	2.27 ± 0.84	2.05 ± 0.57

No statistical analysis provided for 5-hydroxy Saxagliptin Tmax

23. Secondary:

Metformin AUC(0-t) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	Metformin AUC(0-t)
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to end of study. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	0
Metformin AUC(0-t) [units: ng*hr/mL] Mean ± Standard Deviation	9734.38 ± 3123.76	8846.36 ± 3304.75

Statistical Analysis 1 for Metformin AUC(0-t)

Groups ^[1]	Treatment A vs. Treatment B
ratio of geometric least squares means ^[2]	0.906
90% Confidence Interval	( 0.848 to 0.968 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant estimation information:
	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.

Statistical Analysis 2 for Metformin AUC(0-t)

Groups ^[1]	Treatment B
Geometric least squares mean (ng*hr/mL) ^[2]	8377.8

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares means for Treatment B
[2]	Other relevant estimation information:
	No text entered.

Statistical Analysis 3 for Metformin AUC(0-t)

Groups ^[1]	Treatment A
Geometric least squares mean (ng*hr/mL) ^[2]	9246.8

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Geometric least squares mean for Treatment A
[2]	Other relevant estimation information:
	No text entered.

24. Secondary:

Metformin AUC(0-tau) [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Metformin AUC(0-tau)
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Metformin AUC(0-tau) [units: ng*hr/mL] Mean ± Standard Deviation			9501.81 ± 4001.00

No statistical analysis provided for Metformin AUC(0-tau)

25. Secondary:

Metformin Cmin [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Metformin Cmin
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Metformin Cmin [units: ng/mL] Mean ± Standard Deviation			105.04 ± 88.09

No statistical analysis provided for Metformin Cmin

26. Secondary:

Metformin Cavg [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Metformin Cavg
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Metformin Cavg [units: ng/mL] Mean ± Standard Deviation			395.91 ± 166.71

No statistical analysis provided for Metformin Cavg

27. Secondary:

Metformin Fluctuation % [ Time Frame: Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4. ]

Measure Type	Secondary
Measure Title	Metformin Fluctuation %
Measure Description	No text entered.
Time Frame	Period 3: predosing on Days 2 and 3; predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, and 24 hours postdosing on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	0	0	14
Metformin Fluctuation % [units: percentage of fluctuation] Mean ± Standard Deviation			240.06 ± 73.54

No statistical analysis provided for Metformin Fluctuation %

28. Secondary:

Metformin T1/2 [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	Metformin T1/2
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to the end of study. One participant in Treatment A was excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for the terminal phase concentration data. Treatment C was administered only during Period 3, and this outcome measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	28	30	0
Metformin T1/2 [units: ng*hr/mL] Mean ± Standard Deviation	13.02 ± 6.15	12.94 ± 6.74

No statistical analysis provided for Metformin T1/2

29. Secondary:

Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) [ Time Frame: Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing. ]

Measure Type	Secondary
Measure Title	Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])
Measure Description	No text entered.
Time Frame	Periods 1 and 2: predosing, 15, 30, 45 minutes and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36 and 48 hours postdosing.
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.
All treated participants not discontinuing prior to end of study. 2 participants in Treatment A & 1 in Treatment B were excluded as a result of the inability to estimate with acceptable accuracy a terminal slope for terminal phase concentration data. Treatment C was administered only during Period 3, & this measure was analyzed for Periods 1 and 2.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	27	29	0
Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf]) [units: ratio] Mean ± Standard Deviation	0.967 ± 0.029	0.963 ± 0.034

No statistical analysis provided for Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])

30. Secondary:

Metformin Tmax [ Time Frame: Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4. ]

Measure Type	Secondary
Measure Title	Metformin Tmax
Measure Description	No text entered.
Time Frame	Periods 1 & 2:predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24, 36, 48 hours postdose. Period 3: predose on Days 2 & 3; predose, 15, 30, 45 minutes, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 12, 18, 24 hours postdose on Day 4.
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.
All treated participants not discontinuing prior to end of study.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Metformin Tmax [units: hour] Mean ± Standard Deviation	4.38 ± 0.73	4.84 ± 0.91	5.00 ± 1.30

No statistical analysis provided for Metformin Tmax

31. Secondary:

Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) [ Time Frame: AEs: from initiation of study drug administration on morning of Day 1/Period 1 through study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or participation in study if last scheduled visit occurred later. ]

Measure Type	Secondary
Measure Title	Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Measure Description	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition in a subject administered an investigational product and that does not necessarily have a causal relationship with this treatment. SAE=any untoward medical occurrence that results in death, is life-threatening, requires or prolongs inpatient hospitalization (including elective surgery), results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Time Frame	AEs: from initiation of study drug administration on morning of Day 1/Period 1 through study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or participation in study if last scheduled visit occurred later.
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 subjects who received at least one dose of study medication.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs) [units: participants]
Number of Participants With At Least 1 AE	3	3	4
Discontinuation Due to AE	0	0	0
Deaths	0	0	0
SAEs	0	0	0

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

32. Secondary:

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities [ Time Frame: From Day 1 of Period 1 to Day 3 of Period 2 for participants in Treatment Sequence BA and Day 5 of Period 3 for participants in Treatment Sequence ABC ]

Measure Type	Secondary
Measure Title	Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Measure Description	Abnormalities considered clinically significant and/or reported as an AE by the investigator.
Time Frame	From Day 1 of Period 1 to Day 3 of Period 2 for participants in Treatment Sequence BA and Day 5 of Period 3 for participants in Treatment Sequence ABC
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 subjects who received at least one dose of study medication.

Reporting Groups

	Description
Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Measured Values

	Treatment A	Treatment B	Treatment C
Number of Participants Analyzed [units: participants]	29	30	14
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities [units: participants]
Clinical Laboratory Abnormalities	0	0	0
Vital Sign Abnormalities	0	0	0
Physical Examination Abnormalities	0	0	1
12-Lead ECG Abnormalities	0	0	0

No statistical analysis provided for Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities

Serious Adverse Events

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Other Adverse Events

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More Information

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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: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

No publications provided by Bristol-Myers Squibb

Publications automatically indexed to this study:

Boulton DW, Smith CH, Li L, Huang J, Tang A, LaCreta FP. Bioequivalence of saxagliptin/metformin extended-release (XR) fixed-dose combination tablets and single-component saxagliptin and metformin XR tablets in healthy adult subjects. Clin Drug Investig. 2011;31(9):619-30.

Responsible Party:	Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT01192152 History of Changes
Other Study ID Numbers:	CV181-112
Study First Received:	August 30, 2010
Results First Received:	March 9, 2011
Last Updated:	April 19, 2011
Health Authority:	United States: Food and Drug Administration

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