Trial Outcomes & Findings for 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 (NCT NCT01192152)
NCT ID: NCT01192152
Last Updated: 2015-05-12
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
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.
Results posted on
2015-05-12
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|---|
|
Period 1
STARTED
|
15
|
15
|
|
Period 1
COMPLETED
|
15
|
14
|
|
Period 1
NOT COMPLETED
|
0
|
1
|
|
Period 2
STARTED
|
15
|
14
|
|
Period 2
COMPLETED
|
15
|
14
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
|
Period 3
STARTED
|
15
|
0
|
|
Period 3
COMPLETED
|
14
|
0
|
|
Period 3
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|---|
|
Period 1
left prematurely (while on treatment B)
|
0
|
1
|
|
Period 3
family emergency
|
1
|
0
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
All Enrolled and Treated Participants
n=30 Participants
|
|---|---|
|
Age, Continuous
|
31.6 years
STANDARD_DEVIATION 7.76 • n=99 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
13 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
White
|
22 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
8 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
13 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
17 participants
n=99 Participants
|
|
Height
|
166.85 cm
STANDARD_DEVIATION 9.02 • n=99 Participants
|
|
Weight
|
71.56 kg
STANDARD_DEVIATION 9.39 • n=99 Participants
|
|
Body Mass Index
|
25.69 kg/m^2
STANDARD_DEVIATION 2.70 • n=99 Participants
|
PRIMARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
|
99.45 ng*hr/mL
Standard Deviation 18.34
|
105.28 ng*hr/mL
Standard Deviation 23.14
|
—
|
PRIMARY outcome
Timeframe: 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 4Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Observed Maximum Plasma Concentration (Cmax)
|
25.28 ng/mL
Standard Deviation 6.40
|
25.75 ng/mL
Standard Deviation 6.92
|
25.75 ng/mL
Standard Deviation 7.13
|
PRIMARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=27 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=29 Participants
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.
|
|---|---|---|---|
|
Metformin AUC(0-inf)
|
10336.18 ng*hr/mL
Standard Deviation 3066.13
|
9211.29 ng*hr/mL
Standard Deviation 3364.24
|
—
|
PRIMARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin Cmax
|
1184.07 ng/mL
Standard Deviation 276.12
|
1078.67 ng/mL
Standard Deviation 221.72
|
979.93 ng/mL
Standard Deviation 267.58
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])
|
97.76 ng*hr/mL
Standard Deviation 17.96
|
103.34 ng*hr/mL
Standard Deviation 22.73
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Dosing interval = 24 hours.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 to the End of the Dosing Interval (AUC[0-tau])
|
—
|
—
|
19.20 ng*hr/mL
Standard Deviation 20.68
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Trough (Predose) Plasma Concentration (Cmin)
|
—
|
—
|
0.28 ng/mL
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Average Plasma Concentration Over the Dosing Period (Cavg)
|
—
|
—
|
4.13 ng/mL
Standard Deviation 0.86
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Degree of Fluctuation Over the Dosing Interval (Fluctuation %)
|
—
|
—
|
611.85 percentage of fluctuation
Standard Deviation 107.36
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Saxagliptin Terminal Half-life (T1/2)
|
8.69 ng*hr/mL
Standard Deviation 3.71
|
8.85 ng*hr/mL
Standard Deviation 4.47
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])
|
0.981 ratio
Standard Deviation 0.010
|
0.982 ratio
Standard Deviation 0.008
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Saxagliptin Time to Achieve the Observed Maximum Plasma Concentration (Tmax)
|
1.88 hour
Standard Deviation 0.87
|
1.51 hour
Standard Deviation 0.64
|
1.35 hour
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin AUC(0-inf)
|
298.80 ng*hr/mL
Standard Deviation 69.32
|
296.99 ng*hr/mL
Standard Deviation 69.35
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin AUC(0-t)
|
293.06 ng*hr/mL
Standard Deviation 68.28
|
289.37 ng*hr/mL
Standard Deviation 68.72
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin AUC(0-tau)
|
—
|
—
|
318.47 ng*hr/mL
Standard Deviation 54.95
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin Cmax
|
54.69 ng/mL
Standard Deviation 17.00
|
51.32 ng/mL
Standard Deviation 16.19
|
59.87 ng/mL
Standard Deviation 13.83
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin Cmin
|
—
|
—
|
1.51 ng/mL
Standard Deviation 0.22
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin Cavg
|
—
|
—
|
13.27 ng/mL
Standard Deviation 2.29
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin Fluctuation %
|
—
|
—
|
437.09 percentage of fluctuation
Standard Deviation 43.97
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin T1/2
|
13.48 ng*hr/mL
Standard Deviation 1.78
|
13.82 ng*hr/mL
Standard Deviation 2.52
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin AUC(0-t)/AUC(0-inf)
|
0.975 ratio
Standard Deviation 0.009
|
0.973 ratio
Standard Deviation 0.010
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
5-hydroxy Saxagliptin Tmax
|
2.69 hour
Standard Deviation 0.80
|
2.27 hour
Standard Deviation 0.84
|
2.05 hour
Standard Deviation 0.57
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Metformin AUC(0-t)
|
9734.38 ng*hr/mL
Standard Deviation 3123.76
|
8846.36 ng*hr/mL
Standard Deviation 3304.75
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin AUC(0-tau)
|
—
|
—
|
9501.81 ng*hr/mL
Standard Deviation 4001.00
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin Cmin
|
—
|
—
|
105.04 ng/mL
Standard Deviation 88.09
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin Cavg
|
—
|
—
|
395.91 ng/mL
Standard Deviation 166.71
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
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
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin Fluctuation %
|
—
|
—
|
240.06 percentage of fluctuation
Standard Deviation 73.54
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=28 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
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.
|
|---|---|---|---|
|
Metformin T1/2
|
13.02 ng*hr/mL
Standard Deviation 6.15
|
12.94 ng*hr/mL
Standard Deviation 6.74
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Outcome measures
| Measure |
Treatment A
n=27 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=29 Participants
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.
|
|---|---|---|---|
|
Metformin AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])
|
0.967 ratio
Standard Deviation 0.029
|
0.963 ratio
Standard Deviation 0.034
|
—
|
SECONDARY outcome
Timeframe: 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.Population: All treated participants not discontinuing prior to end of study.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Metformin Tmax
|
4.38 hour
Standard Deviation 0.73
|
4.84 hour
Standard Deviation 0.91
|
5.00 hour
Standard Deviation 1.30
|
SECONDARY outcome
Timeframe: 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.Population: All subjects who received at least one dose of study medication.
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.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Number of Participants With At Least 1 AE
|
3 participants
|
3 participants
|
4 participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Discontinuation Due to AE
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Deaths
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
SAEs
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 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 ABCPopulation: All subjects who received at least one dose of study medication.
Abnormalities considered clinically significant and/or reported as an AE by the investigator.
Outcome measures
| Measure |
Treatment A
n=29 Participants
Treatment A: 5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Treatment B
n=30 Participants
Treatment B: Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Treatment C
n=14 Participants
Treatment C: FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Clinical Laboratory Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Vital Sign Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Physical Examination Abnormalities
|
0 participants
|
0 participants
|
1 participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
12-Lead ECG Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Saxa 5mg + 2x500mg Metformin, Fed
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Saxa 5mg/1000mg Metformin, Fed
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Saxa 5mg/500mg Metformin, Fed 4 Days
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Saxa 5mg + 2x500mg Metformin, Fed
n=29 participants at risk
5 mg saxagliptin + 2 Glucophage XR 500 mg tablets, single dose under fed conditions
|
Saxa 5mg/1000mg Metformin, Fed
n=30 participants at risk
Fixed dose combination (FDC) tablet (5 mg saxagliptin + 1000 mg metformin XR), single dose, under fed conditions
|
Saxa 5mg/500mg Metformin, Fed 4 Days
n=14 participants at risk
FDC tablet (5 mg saxagliptin + 1000 mg metformin XR), once daily for 4 days, under fed conditions.
|
|---|---|---|---|
|
Nervous system disorders
HEADACHE
|
0.00%
0/29
|
6.7%
2/30
|
0.00%
0/14
|
|
Nervous system disorders
DIZZINESS
|
3.4%
1/29
|
0.00%
0/30
|
0.00%
0/14
|
|
Gastrointestinal disorders
NAUSEA
|
3.4%
1/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Gastrointestinal disorders
DRY MOUTH
|
3.4%
1/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Gastrointestinal disorders
TOOTHACHE
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Gastrointestinal disorders
CONSTIPATION
|
3.4%
1/29
|
0.00%
0/30
|
0.00%
0/14
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Gastrointestinal disorders
APHTHOUS STOMATITIS
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Infections and infestations
GASTROENTERITIS
|
0.00%
0/29
|
3.3%
1/30
|
0.00%
0/14
|
|
Renal and urinary disorders
DYSURIA
|
0.00%
0/29
|
0.00%
0/30
|
14.3%
2/14
|
|
Skin and subcutaneous tissue disorders
ACNE
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Reproductive system and breast disorders
VAGINAL DISCHARGE
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Reproductive system and breast disorders
VULVOVAGINAL PRURITUS
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
PAIN IN EXTREMITY
|
0.00%
0/29
|
0.00%
0/30
|
7.1%
1/14
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER