Bioequivalence Study of the Fixed Dose Combination of 5 m... | NCT01192152

Label	Type	Description	Intervention Names
5 mg saxagliptin + 2 Glucophage XR 500 mg tablet	Experimental		Drug: saxagliptin Drug: Glucophage XR
FDC tablet (5 mg saxa + 1000 mg metformin XR) (single dose)	Experimental	under fed state, single dose	Drug: saxagliptin + metformin XR (FDC tablet)
FDC tablet (5 mg saxa + 1000 mg metformin XR) (4 days)	Experimental	under fed state, 4 days	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 + 2 Glucophage XR 500 mg tablet

Measure	Description	Time Frame
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])		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.
Saxagliptin Observed Maximum Plasma Concentration (Cmax)		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
Metformin AUC(0-inf)		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.
Metformin Cmax		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	Description	Time Frame
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])		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.
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])

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

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.

ID	Title	Description
FG000	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.

Primary

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

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants	OG00028 OG00130 OG0020

Title

Denominators

Categories

Title	Measurements
	OG00099.45± 18.34 OG001105.28± 23.14

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 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.					Ratio of geometric least squares means	1.045			2-Sided	90	1.025	1.065			Ratio = Treatment B/Treatment A. Geometric least squares means values presented in other statistical analysis entries.	Yes

Secondary

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

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])

Dosing interval = 24 hours.

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Primary

Saxagliptin Observed Maximum Plasma Concentration (Cmax)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Saxagliptin Trough (Predose) Plasma Concentration (Cmin)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

percentage of fluctuation

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Saxagliptin Terminal Half-life (T1/2)

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

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

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.

Posted

Mean

Standard Deviation

ratio

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Secondary

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

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

hour

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin AUC(0-inf)

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

5-hydroxy Saxagliptin AUC(0-t)

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin AUC(0-tau)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin Cmax

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin Cmin

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin Cavg

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin Fluctuation %

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

percentage of fluctuation

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

5-hydroxy Saxagliptin T1/2

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf)

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.

Posted

Mean

Standard Deviation

ratio

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

5-hydroxy Saxagliptin Tmax

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

hour

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Primary

Metformin AUC(0-inf)

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

Metformin AUC(0-t)

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Metformin AUC(0-tau)

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Primary

Metformin Cmax

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Metformin Cmin

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants	OG000

Secondary

Metformin Cavg

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

ng/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants	OG000

Secondary

Metformin Fluctuation %

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

percentage of fluctuation

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts
Participants

Secondary

Metformin T1/2

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.

Posted

Mean

Standard Deviation

ng*hr/mL

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Secondary

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

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.

Posted

Mean

Standard Deviation

ratio

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Secondary

Metformin Tmax

All treated participants not discontinuing prior to end of study.

Posted

Mean

Standard Deviation

hour

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed 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.

All subjects who received at least one dose of study medication.

Posted

Number

participants

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.

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C

Secondary

Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities

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

All subjects who received at least one dose of study medication.

Posted

Number

participants

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

ID	Title	Description
OG000	Treatment A	Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
OG001	Treatment B	Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
OG002	Treatment C	Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.

Units	Counts

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
HEADACHE	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0012 affected30 at risk EG0020 affected14 at risk
DIZZINESS	Nervous system disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected29 at risk EG0010 affected30 at risk EG0020 affected14 at risk
NAUSEA	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
DRY MOUTH	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
TOOTHACHE	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
CONSTIPATION	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0001 affected29 at risk EG0010 affected30 at risk EG0020 affected14 at risk
ABDOMINAL PAIN	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
APHTHOUS STOMATITIS	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
ABDOMINAL DISTENSION	Gastrointestinal disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
GASTROENTERITIS	Infections and infestations	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0011 affected30 at risk EG0020 affected14 at risk
DYSURIA	Renal and urinary disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0022 affected14 at risk
ACNE	Skin and subcutaneous tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
VAGINAL DISCHARGE	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
VULVOVAGINAL PRURITUS	Reproductive system and breast disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
BACK PAIN	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk
PAIN IN EXTREMITY	Musculoskeletal and connective tissue disorders	MedDRA 12.0	Systematic Assessment	EG0000 affected29 at risk EG0010 affected30 at risk EG0021 affected14 at risk

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

ID	Title	Description	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Saxa 5mg + 2x500mg Metformin, Fed	5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions	29	3	29
EG001	Saxa 5mg/1000mg Metformin, Fed	Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions	30	3	30
EG002	Saxa 5mg/500mg Metformin, Fed 4 Days	FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.	14	4	14