Bioequivalence Study of the Fixed Dose Combination of 5 m... | NCT01192139

Bioequivalence Study of the Fixed Dose Combination of 5 m... | NCT01192139 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
5 mg saxagliptin + a single 500 mg metformin XR tablet	Experimental		Drug: saxagliptin Drug: metformin XR
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fed)	Experimental	under fed state	Drug: saxagliptin + metformin XR (FDC tablet)
FDC tablet (5 mg saxagliptin + 500 mg metformin XR) (Fasting)	Experimental	under fasted state	Drug: saxagliptin + metformin XR (FDC tablet)

Name	Type	Description	Arm Group Labels	Other Names
saxagliptin	Drug	Tablets, Oral, 5 mg, once daily, Single dose	5 mg saxagliptin + a single 500 mg metformin XR tablet

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])	Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant	Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)
Saxagliptin Observed Maximum Plasma Concentration (Cmax)		Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)
Metformin AUC(0-inf)	Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant	Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)
Metformin Cmax		Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

Secondary Outcomes

Measure	Description	Time Frame
Saxagliptin Terminal Half-life (T1/2)	terminal half life; calculated as ln(2)/Kel	Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])

Eligibility Module

Contacts/Locations Module

Name	Affiliation	Role
Bristol-Myers Squibb	Bristol-Myers Squibb	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Ppd Development, Lp		Austin	Texas	78744	United States

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21819160	Derived	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. doi: 10.2165/11590290-000000000-00000.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Treatment Sequence ABC	Treatment A (period 1): 5 mg saxagliptin + a single 500 mg metformin XR tablet; Treatment B (period 2): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions; Treatment C (period 3): FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions. Participants underwent at least a 3-day washout period between each treatment.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Period 2

Type	Comment	Milestone Data
STARTED		FG0005 subjects FG0015 subjects FG0025 subjects FG0035 subjects FG0045 subjects FG0055 subjects
COMPLETED		FG0005 subjects FG0015 subjects FG0025 subjects FG0035 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

Period 3

Type	Comment	Milestone Data
STARTED		FG0005 subjects FG0015 subjects FG0025 subjects FG0035 subjects FG0045 subjects FG0055 subjects
COMPLETED		FG0005 subjects FG0015 subjects FG0025 subjects FG0035 subjects FG004
NOT COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004

ID	Title	Description
BG000	All Enrolled and Treated Participants

Units	Counts
Participants	BG00030

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00029.1± 8.0

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00014
Male	BG00016

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

White

Title	Measurements
	BG00017

Black or African American

Title	Measurements
	BG000

Race/Ethnicity, Customized

Number

participants

Title

Denominators

Categories

Hispanic or Latino

Title	Measurements
	BG0009

Not Hispanic or Latino

Title	Measurements
	BG000

Height

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG000170.0± 9.22

Weight

Mean

Standard Deviation

Title

Denominators

Categories

Title	Measurements
	BG00078.31± 13.74

Body Mass Index

Mean

Standard Deviation

kg/m^2

Title

Denominators

Categories

Title	Measurements
	BG00026.97± 3.07

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

Area under the plasma concentration versus time curve from time 0 extrapolated to infinity; calculated as AUC0-t [calculated using the linear trapezoidal rule] + Ct/Kel, where Ct was the last measurable concentration and Kel was the terminal rate constant

All treated participants

Posted

Mean

Standard Deviation

ng*hr/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants	OG00030 OG00130 OG00230

Title

Denominators

Categories

Title	Measurements
	OG000107.28± 25.13 OG001111.72± 26.55 OG002103.35± 23.15

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of a saxagliptin tablet and a metformin XR tablet 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, respectively.					Ratio of Geometric Least Squares Means	1.039			2-Sided	90	1.011	1.068			Ratio=Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	Yes

Secondary

Saxagliptin Terminal Half-life (T1/2)

terminal half life; calculated as ln(2)/Kel

All treated participants

Posted

Mean

Standard Deviation

hours

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

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

Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.

All treated participants

Posted

Mean

Standard Deviation

ng*hr/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Primary

Saxagliptin Observed Maximum Plasma Concentration (Cmax)

All treated participants

Posted

Mean

Standard Deviation

ng/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)

All treated participants

Posted

Mean

Standard Deviation

hours

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])

All treated participants

Posted

Mean

Standard Deviation

ratio

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Active Metabolite BMS-510849 AUC(0-inf)

All treated participants

Posted

Mean

Standard Deviation

ng*hr/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Secondary

Active Metabolite BMS-510849 AUC(0-t)

Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.

All treated participants

Posted

Mean

Standard Deviation

ng*hr/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts

Secondary

Active Metabolite BMS-510849 Cmax

All treated participants

Posted

Mean

Standard Deviation

ng/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Active Metabolite BMS-510849 T1/2

terminal half life; calculated as ln(2)/Kel

All treated participants

Posted

Mean

Standard Deviation

hours

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Active Metabolite BMS-510849 Tmax

All treated participants

Posted

Mean

Standard Deviation

hours

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)

All treated participants

Posted

Mean

Standard Deviation

ratio

Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Primary

Metformin AUC(0-inf)

Treated participants (the smaller sample size for AUC[0-inf] was due to the inability to estimate potassium chloride for some participants)

Posted

Mean

Standard Deviation

ng*hr/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Secondary

Metformin AUC(0-t)

Area under the plasma concentration versus time curve from time 0 to the time of the last quantifiable concentration (Ct), calculated using the linear trapezoidal rule.

All treated participants

Posted

Mean

Standard Deviation

ng*hr/mL

Period 1 (samples taken before dosing, and at 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts

Primary

Metformin Cmax

All treated participants

Posted

Mean

Standard Deviation

ng/mL

Periods 1, 2, and 3 (samples taken before dosing, and at 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Metformin T1/2

terminal half life; calculated as ln(2)/Kel

Treated participants (the smaller sample size for T1/2 was due to the inability to estimate Kel for some of the subjects).

Posted

Mean

Standard Deviation

hours

Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Metformin Tmax

All treated participants

Posted

Mean

Standard Deviation

hours

Periods 1, 2, and 3 (before dosing, 0.167, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 10, 12, 18, 24, 36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants	OG000

Secondary

Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])

Treated participants (the smaller sample size for AUC(0-inf) was due to the inability to estimate Kel for some of the subjects).

Posted

Mean

Standard Deviation

ratio

Period 1 (before dosing, 0.167,0.25,0.5,0.75,1,1.5,2,3,4,5,6,7,8,10,12,18,24,36 and 48 hours after dosing)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Secondary

Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)

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.

Safety Population = all participants who received any study drug.

Posted

Number

Participants

AEs: from initiation of study drug administration on Day 1/Period 1 through study discharge Day 3/Period 3. SAEs: from date of written consent until 30 days after discontinuation of dosing or participation in study if last scheduled visit occurred later.

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting

Secondary

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities

Abnormalities considered by the investigator to be clinically significant and/or reported as an AE.

Safety Population

Posted

Number

Participants

From Day 1 of Period 1 through Day 3 of Period 3 (study discharge)

ID	Title	Description
OG000	Treatment A - Saxagliptin + Metformin XR, Fed	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
OG001	Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed	fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
OG002	Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Treatment A	5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions	30	3	30
EG001	Treatment C	FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions	30	4	30
EG002	Treatment B	Fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions	30	2	30

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
HEADACHE	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0021 affected30 at risk
PRESYNCOPE	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0020 affected30 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0020 affected30 at risk
DIARRHOEA	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0021 affected30 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0020 affected30 at risk
FLATULENCE	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0010 affected30 at risk EG0021 affected30 at risk
CHAPPED LIPS	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0011 affected30 at risk EG0020 affected30 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0010 affected30 at risk EG0021 affected30 at risk
LIP SWELLING	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected30 at risk EG0010 affected30 at risk EG0020 affected30 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected30 at risk EG0010 affected30 at risk EG0021 affected30 at risk
DYSURIA	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected30 at risk EG0010 affected30 at risk EG0020 affected30 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected30 at risk EG0011 affected30 at risk EG0020 affected30 at risk

Group IDs	Group Description	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001		Ratio of Geometric Least Squares Mean	1.039	2-Sided	90	1.011	1.068	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	No	Superiority or Other
OG001 OG002		Ratio of Geometric Least Squares Means	1.080	2-Sided	90	1.051	1.110	Ratio=Treatment B/Treatment C. Geometric least squares means values are presented in other statistical analysis entries.	No	Superiority or Other
OG000	Geometric least squares mean for treatment A	Geometric least squares mean (ng*hr/mL)	102.84		95				No	Superiority or Other
OG001	Geometric least squares mean for treatment B	Geometric least squares mean (ng*hr/mL)	106.89		95				No	Superiority or Other
OG002	Geometric least squares mean for treatment C	Geometric least squares mean (ng*hr/mL)	98.99		95				No	Superiority or Other

Group IDs	Group Description	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	If there was no difference between the bioavailabilities of saxagliptin from the FDC tablet versus saxagliptin from coadministration of a saxagliptin tablet and a metformin XR tablet 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, respectively.	Ratio of Geometric Least Squares Means	1.021	2-Sided	90	0.940	1.109	Ratio=Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	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.
OG001 OG002		Ratio of Geometric Least Squares Means	0.949	2-Sided	90	0.873	1.031	Ratio = Treatment B/Treatment C. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	Lack of food effect was concluded if the fed to fasted ratios of geometric means were entirely contained within (80%, 125%) for both Cmax and AUC(INF) of saxagliptin.
OG000	Geometric least squares mean for treatment A	Geometric least squares mean (ng*hr/mL)	25.68		95				No	Superiority or Other
OG001	Geometric least squares mean for treatment B	Geometric least squares mean (ng*hr/mL)	26.21		95				No	Superiority or Other
OG002	Geometric least squares mean for treatment C	Geometric least squares mean (ng*hr/mL)	27.63		95				No	Superiority or Other

Group IDs	Group Description	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a saxagliptin tablet and a metformin XR tablet 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 96% and 97% power to conclude BE with respect to Cmax and AUC0-inf, respectively.	Ratio of Least Squares Geometric Means	0.915	2-Sided	90	0.836	1.002	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	BE concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within (80%, 125%) for both Cmax and AUC(INF) of saxagliptin and metformin.
OG001 OG002		Ratio of Geometric LS Mean and 90% CI	1.010	2-Sided	90	0.918	1.111	Ratio = Treatment B/Treatment C. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	lack of food effect concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within (80%, 125%) for both Cmax and AUC(INF) of saxagliptin and metformin.
OG000	Geometric least squares means for treatment A	Geometric least squares mean (ng*hr/mL)	5542.2		95				No	Superiority or Other
OG001	Geometric least squares mean for treatment B	Geometric least squares mean (ng*hr/mL)	5072.9		95				No	Superiority or Other
OG002	Geometric least squares mean for treatment C	Geometric least squares mean (ng*hr/mL)	5023.3		95				No	Superiority or Other

Group IDs	Group Description	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type
OG000 OG001		Ratio of Geometric Least Squares Mean	0.920	2-Sided	90	0.854	0.992	Ratio=Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	No	Superiority or Other
OG001 OG002		Ratio of Geometric Least Squares Means	1.025	2-Sided	95	0.951	1.105	Ratio=Treatment B/Treatment C. Geometric least squares means values are presented in other statistical analysis entries.	No	Superiority or Other
OG000	Geometric least squares means for treatment A	Geometric least squares mean (ng*hr/mL)	5287.1		95				No	Superiority or Other
OG001	Geometric least squares mean for treatment B	Geometric least squares mean (ng*hr/mL)	4866.2		95				No	Superiority or Other
OG002	Geometric least squares means for treatment C	Geometric least squares mean (ng*hr/mL)	4746.8		95				No	Superiority or Other

Group IDs	Group Description	Parameter Type	Parameter Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment
OG000 OG001	If there was no difference between the bioavailabilities of metformin from the FDC tablet versus metformin from coadministration of a metformin XR tablet 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 96% and 97% power to conclude BE with respect to Cmax and AUC0-inf, respectively.	Ratio of Geometric Least Squares Means	0.933	2-Sided	95	0.865	1.007	Ratio = Treatment B/Treatment A. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	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.
OG001 OG002		Ratio of Geometric Least Squares Means	0.898	2-Sided	90	0.832	0.969	Ration = Treatment B/Treatment C. Geometric least squares means values are presented in other statistical analysis entries.	Yes	Non-Inferiority or Equivalence	Lack of food effect was concluded if the 90% CIs for the test-to-reference ratios of geometric means were entirely contained within (80%, 125%) for both Cmax and AUC(inf) of saxagliptin and metformin.
OG000	Geometric least squares mean for treatment A	Geometric least squares mean (ng*hr/mL)	608.41		95				No	Superiority or Other
OG001	Geometric least squares mean for treatment B	Geometric least squares mean (ng*hr/mL)	567.85		95				No	Superiority or Other
OG002	Geometric least squares mean for treatment C	Geometric least squares mean (ng*hr/mL)	632.39		95				No	Superiority or Other

Title

Denominators

Categories

Number of Participants With At Least 1 AE

Title	Measurements
	OG0003 OG0012 OG0024

Discontinuation Due to an AE

Title	Measurements
	OG0000 OG0010 OG0020

Deaths

Title	Measurements
	OG0000 OG0010 OG0020

SAEs

Title	Measurements
	OG0000 OG0010 OG0020

Title

Denominators

Categories

Clinical Laboratory Abnormalities

Title	Measurements
	OG0000 OG0010 OG0020

Vital Sign Abnormalities

Title	Measurements
	OG0000 OG0010 OG0020

Physical Examination Abnormalities

Title	Measurements
	OG0000 OG0010 OG0020

12-Lead ECG Abnormalities

Title	Measurements
	OG0000 OG0010 OG0020

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals