Trial Outcomes & Findings for Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN) (NCT NCT01192139)
NCT ID: NCT01192139
Last Updated: 2015-05-21
Results Overview
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
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
30 participants
Primary outcome timeframe
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)
Results posted on
2015-05-21
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 6 treatment sequences.
Participant milestones
| Measure |
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.
|
Treatment Sequence ACB
Treatment A (period 1): 5 mg saxagliptin + a single 500 mg metformin XR tablet; Treatment C (period 2): FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions; Treatment B (period 3): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions. Participants underwent at least a 3-day washout period between each treatment.
|
Treatment Sequence BAC
Treatment B (period 1): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions; Treatment A (period 2): 5 mg saxagliptin + a single 500 mg metformin XR tablet; 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.
|
Treatment Sequence BCA
Treatment B (period 1): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions; Treatment C (period 2): FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions; Treatment A (period 3): 5 mg saxagliptin + a single 500 mg metformin XR tablet. Participants underwent at least a 3-day washout period between each treatment.
|
Treatment Sequence CAB
Treatment C (period 1): FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions; Treatment A (period 2): 5 mg saxagliptin + a single 500 mg metformin XR tablet; Treatment B (period 3): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions. Participants underwent at least a 3-day washout period between each treatment.
|
Treatment Sequence CBA
Treatment C (period 1): FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions; Treatment B (period 2): fixed-dose combination (FDC) Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions; Treatment A (period 3): 5 mg saxagliptin + a single 500 mg metformin XR tablet. Participants underwent at least a 3-day washout period between each treatment.
|
|---|---|---|---|---|---|---|
|
Period 1
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 1
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 2
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 3
COMPLETED
|
5
|
5
|
5
|
5
|
5
|
5
|
|
Period 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Bioequivalence Study of the Fixed Dose Combination of 5 mg Saxagliptin and 500 mg Metformin XR Tablet (Manufactured in Mt Vernon, IN) Relative to 5 mg Saxagliptin Tablet and 500 mg Metformin XR Tablet (Manufactured in Evansville, IN)
Baseline characteristics by cohort
| Measure |
All Enrolled and Treated Participants
n=30 Participants
|
|---|---|
|
Age, Continuous
|
29.1 years
STANDARD_DEVIATION 8.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
17 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
12 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
9 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
21 participants
n=5 Participants
|
|
Height
|
170.0 cm
STANDARD_DEVIATION 9.22 • n=5 Participants
|
|
Weight
|
78.31 kg
STANDARD_DEVIATION 13.74 • n=5 Participants
|
|
Body Mass Index
|
26.97 kg/m^2
STANDARD_DEVIATION 3.07 • n=5 Participants
|
PRIMARY outcome
Timeframe: 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)Population: All treated participants
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
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Saxagliptin Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
|
103.35 ng*hr/mL
Standard Deviation 23.15
|
107.28 ng*hr/mL
Standard Deviation 25.13
|
111.72 ng*hr/mL
Standard Deviation 26.55
|
PRIMARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Saxagliptin Observed Maximum Plasma Concentration (Cmax)
|
28.85 ng/mL
Standard Deviation 8.62
|
26.84 ng/mL
Standard Deviation 8.26
|
27.25 ng/mL
Standard Deviation 7.95
|
PRIMARY outcome
Timeframe: 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)Population: Treated participants (the smaller sample size for AUC\[0-inf\] was due to the inability to estimate potassium chloride for some participants)
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
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=23 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=25 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=24 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin AUC(0-inf)
|
5073.70 ng*hr/mL
Standard Deviation 1406.45
|
5865.92 ng*hr/mL
Standard Deviation 2357.15
|
5516.97 ng*hr/mL
Standard Deviation 2423.08
|
PRIMARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin Cmax
|
657.23 ng/mL
Standard Deviation 187.67
|
629.73 ng/mL
Standard Deviation 160.14
|
586.87 ng/mL
Standard Deviation 150.63
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
terminal half life; calculated as ln(2)/Kel
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Saxagliptin Terminal Half-life (T1/2)
|
9.21 hours
Standard Deviation 3.91
|
8.46 hours
Standard Deviation 2.85
|
8.56 hours
Standard Deviation 3.04
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
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.
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) 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])
|
101.52 ng*hr/mL
Standard Deviation 23.01
|
105.47 ng*hr/mL
Standard Deviation 24.98
|
109.88 ng*hr/mL
Standard Deviation 26.36
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Time to Achieve the Observed Maximum Saxagliptin Plasma Concentration (Tmax)
|
0.65 hours
Standard Deviation 0.50
|
1.65 hours
Standard Deviation 0.65
|
1.48 hours
Standard Deviation 0.75
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Saxagliptin Fraction of AUC(0-inf) Contributed by AUC(0-t) (AUC[0-t]/AUC[0-inf])
|
0.982 ratio
Standard Deviation 0.008
|
0.983 ratio
Standard Deviation 0.006
|
0.983 ratio
Standard Deviation 0.006
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
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
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 AUC(0-inf)
|
289.06 ng*hr/mL
Standard Deviation 66.89
|
291.72 ng*hr/mL
Standard Deviation 79.21
|
295.94 ng*hr/mL
Standard Deviation 75.40
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
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.
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 AUC(0-t)
|
281.79 ng*hr/mL
Standard Deviation 65.91
|
284.46 ng*hr/mL
Standard Deviation 78.25
|
289.03 ng*hr/mL
Standard Deviation 74.80
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 Cmax
|
49.09 ng/mL
Standard Deviation 15.46
|
49.71 ng/mL
Standard Deviation 16.94
|
49.28 ng/mL
Standard Deviation 14.59
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
terminal half life; calculated as ln(2)/Kel
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 T1/2
|
14.04 hours
Standard Deviation 1.33
|
13.88 hours
Standard Deviation 1.53
|
13.65 hours
Standard Deviation 1.72
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 Tmax
|
1.46 hours
Standard Deviation 0.70
|
2.38 hours
Standard Deviation 0.76
|
2.42 hours
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Active Metabolite BMS-510849 AUC(0-t)/AUC(0-inf)
|
0.974 ratio
Standard Deviation 0.006
|
0.974 ratio
Standard Deviation 0.008
|
0.975 ratio
Standard Deviation 0.008
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
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.
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin AUC(0-t)
|
4896.95 ng*hr/mL
Standard Deviation 1340.41
|
5617.39 ng*hr/mL
Standard Deviation 2181.99
|
5200.46 ng*hr/mL
Standard Deviation 2203.34
|
SECONDARY outcome
Timeframe: 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)Population: Treated participants (the smaller sample size for T1/2 was due to the inability to estimate Kel for some of the subjects).
terminal half life; calculated as ln(2)/Kel
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=23 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=25 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=24 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin T1/2
|
14.9 hours
Standard Deviation 7.40
|
10.7 hours
Standard Deviation 5.90
|
12.6 hours
Standard Deviation 7.05
|
SECONDARY outcome
Timeframe: 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)Population: All treated participants
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin Tmax
|
4.11 hours
Standard Deviation 0.88
|
4.78 hours
Standard Deviation 1.04
|
4.90 hours
Standard Deviation 1.13
|
SECONDARY outcome
Timeframe: 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)Population: Treated participants (the smaller sample size for AUC(0-inf) was due to the inability to estimate Kel for some of the subjects).
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=23 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=25 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=24 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Metformin Fraction of AUC(0-inf) Contributed by AUC(0-t)(AUC[0-t]/AUC[0-inf])
|
0.965 ratio
Standard Deviation 0.031
|
0.979 ratio
Standard Deviation 0.020
|
0.970 ratio
Standard Deviation 0.026
|
SECONDARY outcome
Timeframe: 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.Population: Safety Population = all participants who received any study drug.
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 C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Number of Participants With At Least 1 AE
|
4 Participants
|
3 Participants
|
2 Participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs)
Discontinuation Due to an 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 through Day 3 of Period 3 (study discharge)Population: Safety Population
Abnormalities considered by the investigator to be clinically significant and/or reported as an AE.
Outcome measures
| Measure |
Treatment C - FDC Tablet (Saxagliptin + Metformin XR), Fasting
n=30 Participants
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment A - Saxagliptin + Metformin XR, Fed
n=30 Participants
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment B - FDC Tablet (Saxagliptin + Metformin XR), Fed
n=30 Participants
fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities
Clinical Laboratory Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities
Vital Sign Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities
Physical Examination Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and Electrocardiogram (ECG) Abnormalities
12-Lead ECG Abnormalities
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment C
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment A
n=30 participants at risk
5 mg saxagliptin tablet + a single 500 mg metformin XR tablet under fed conditions
|
Treatment C
n=30 participants at risk
FDC Tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fasting conditions
|
Treatment B
n=30 participants at risk
Fixed-dose combination (FDC) tablet (5 mg Saxagliptin + 500 mg Metformin XR) under fed conditions
|
|---|---|---|---|
|
Nervous system disorders
HEADACHE
|
0.00%
0/30
|
3.3%
1/30
|
3.3%
1/30
|
|
Nervous system disorders
PRESYNCOPE
|
0.00%
0/30
|
3.3%
1/30
|
0.00%
0/30
|
|
Gastrointestinal disorders
NAUSEA
|
0.00%
0/30
|
3.3%
1/30
|
0.00%
0/30
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/30
|
3.3%
1/30
|
3.3%
1/30
|
|
Gastrointestinal disorders
DRY MOUTH
|
0.00%
0/30
|
3.3%
1/30
|
0.00%
0/30
|
|
Gastrointestinal disorders
FLATULENCE
|
0.00%
0/30
|
0.00%
0/30
|
3.3%
1/30
|
|
Gastrointestinal disorders
CHAPPED LIPS
|
0.00%
0/30
|
3.3%
1/30
|
0.00%
0/30
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/30
|
0.00%
0/30
|
3.3%
1/30
|
|
Gastrointestinal disorders
LIP SWELLING
|
3.3%
1/30
|
0.00%
0/30
|
0.00%
0/30
|
|
Gastrointestinal disorders
ABDOMINAL DISTENSION
|
0.00%
0/30
|
0.00%
0/30
|
3.3%
1/30
|
|
Renal and urinary disorders
DYSURIA
|
3.3%
1/30
|
0.00%
0/30
|
0.00%
0/30
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
3.3%
1/30
|
3.3%
1/30
|
0.00%
0/30
|
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