Trial Outcomes & Findings for Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered (NCT NCT01068743)
NCT ID: NCT01068743
Last Updated: 2015-05-08
Results Overview
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosing
Results posted on
2015-05-08
Participant Flow
Participants (N = 24) who met all of the inclusion and none of the exclusion criteria were recruited from a single site in the United States.
Participants were screened for eligibility within 21 days before Day 1 of period 1. On Day -1 of each period, the participants were admitted to the clinical facility and confined for 4 days. All the 24 participants were randomly assigned to 1 of 4 treatment sequences (ADBC, BACD, CBDA, or DCAB). The washout between each dose was at least 7 days.
Participant milestones
| Measure |
Treatment Sequence ADBC
Treatment A (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment D (period 2): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment B (period 3): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment C (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition.
|
Treatment Sequence BACD
Treatment B (period 1): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment A (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment C (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment D (period 4): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition.
|
Treatment Sequence CBDA
Treatment C (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment B (period 2): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment D (period 3): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment A (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition.
|
Treatment Sequence DCAB
Treatment D (period 1): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment C (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment A (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment B (period 4): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition.
|
|---|---|---|---|---|
|
Period 1
STARTED
|
6
|
6
|
6
|
6
|
|
Period 1
COMPLETED
|
6
|
6
|
6
|
6
|
|
Period 1
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 2
STARTED
|
6
|
6
|
6
|
6
|
|
Period 2
COMPLETED
|
6
|
6
|
6
|
6
|
|
Period 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3
STARTED
|
6
|
6
|
6
|
6
|
|
Period 3
COMPLETED
|
6
|
5
|
6
|
6
|
|
Period 3
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Period 4
STARTED
|
6
|
5
|
6
|
6
|
|
Period 4
COMPLETED
|
6
|
5
|
6
|
6
|
|
Period 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Sequence ADBC
Treatment A (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment D (period 2): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment B (period 3): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment C (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition.
|
Treatment Sequence BACD
Treatment B (period 1): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment A (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment C (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment D (period 4): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition.
|
Treatment Sequence CBDA
Treatment C (period 1): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment B (period 2): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition; Treatment D (period 3): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment A (period 4): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition.
|
Treatment Sequence DCAB
Treatment D (period 1): Fixed dose combination (FDC) tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition; Treatment C (period 2): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fed condition; Treatment A (period 3): 2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition; Treatment B (period 4): FDC tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition.
|
|---|---|---|---|---|
|
Period 3
Adverse Event
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered
Baseline characteristics by cohort
| Measure |
All Enrolled and Treated Participants
n=24 Participants
|
|---|---|
|
Age, Continuous
|
35.5 years
STANDARD_DEVIATION 10.61 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
|
Height
|
170.2 cm
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
Weight
|
79.7 kg
STANDARD_DEVIATION 13.7 • n=5 Participants
|
|
Body Mass Index (BMI)
|
27.4 kg/m^2
STANDARD_DEVIATION 3.05 • n=5 Participants
|
PRIMARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 Extrapolated to Infinity (AUC[0-inf])
|
49.23 ng*hr/mL
Geometric Coefficient of Variation 18.52
|
49.94 ng*hr/mL
Geometric Coefficient of Variation 19.72
|
52.50 ng*hr/mL
Geometric Coefficient of Variation 17.95
|
53.15 ng*hr/mL
Geometric Coefficient of Variation 17.81
|
PRIMARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Observed Maximum Plasma Concentration (Cmax)
|
9.73 ng/mL
Geometric Coefficient of Variation 20.44
|
9.97 ng/mL
Geometric Coefficient of Variation 29.07
|
10.25 ng/mL
Geometric Coefficient of Variation 26.87
|
10.88 ng/mL
Geometric Coefficient of Variation 23.72
|
PRIMARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=23 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Metformin PK Parameter AUC(0-inf)
|
11998.00 ng*hr/mL
Geometric Coefficient of Variation 23.68
|
12271.61 ng*hr/mL
Geometric Coefficient of Variation 20.42
|
11988.30 ng*hr/mL
Geometric Coefficient of Variation 16.94
|
11838.11 ng*hr/mL
Geometric Coefficient of Variation 18.18
|
PRIMARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Metformin PK Parameter Cmax
|
1724.38 ng/mL
Geometric Coefficient of Variation 25.49
|
1715.79 ng/mL
Geometric Coefficient of Variation 23.59
|
1571.21 ng/mL
Geometric Coefficient of Variation 15.64
|
1541.76 ng/mL
Geometric Coefficient of Variation 17.45
|
SECONDARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC (0-inf) is the area under the plasma concentration-time curve from time zero extrapolated to infinite time.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
5-hydroxy Saxagliptin PK Parameter AUC(0-inf)
|
118.58 ng*hr/mL
Geometric Coefficient of Variation 24.08
|
119.54 ng*hr/mL
Geometric Coefficient of Variation 21.16
|
121.99 ng*hr/mL
Geometric Coefficient of Variation 25.42
|
125.54 ng*hr/mL
Geometric Coefficient of Variation 24.82
|
SECONDARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Cmax is the maximum observed concentration of drug substance in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
5-hydroxy Saxagliptin PK Parameter Cmax
|
16.83 ng/mL
Geometric Coefficient of Variation 32.95
|
16.72 ng/mL
Geometric Coefficient of Variation 32.92
|
17.35 ng/mL
Geometric Coefficient of Variation 32.95
|
18.59 ng/mL
Geometric Coefficient of Variation 30.78
|
SECONDARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC\[0-t\] is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
5-hydroxy Saxagliptin PK Parameter Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUC[0-t])
|
109.60 ng*hr/mL
Geometric Coefficient of Variation 25.81
|
110.61 ng*hr/mL
Geometric Coefficient of Variation 22.77
|
113.15 ng*hr/mL
Geometric Coefficient of Variation 26.53
|
117.04 ng*hr/mL
Geometric Coefficient of Variation 25.74
|
SECONDARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
5-hydroxy Saxagliptin PK Parameter Terminal Half-life (T 1/2)
|
7.58 hr
Standard Deviation 1.32
|
7.58 hr
Standard Deviation 1.35
|
7.48 hr
Standard Deviation 1.10
|
7.22 hr
Standard Deviation 1.01
|
SECONDARY outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
5-hydroxy Saxagliptin PK Parameter Time to Achieve the Observed Maximum Plasma Concentration (Tmax)
|
2.21 hr
Standard Deviation 0.75
|
1.86 hr
Standard Deviation 0.71
|
2.65 hr
Standard Deviation 0.83
|
2.46 hr
Standard Deviation 0.72
|
SECONDARY outcome
Timeframe: AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).Population: All participants 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=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).
Number of Participants With at Least 1 AE
|
4 participants
|
5 participants
|
3 participants
|
4 participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).
Discontinuation Due to AE
|
1 participants
|
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
|
0 participants
|
|
Safety: Adverse Events (AEs), Discontinuations Due to AEs, Deaths, and Serious AEs (SAEs).
SAEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: From Day 1/Period 1 to study discharge or premature discontinuation. Duration of study was approximately 45 days (including screening).Population: All participants who received at least one dose of study medication.
Abnormalities that were considered clinically significant and/or reported as an AE by the investigator.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Clinical Laboratory Abnormalities
|
0 participants
|
0 participants
|
1 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
|
0 participants
|
|
Safety: Clinically Significant Laboratory, Vital Sign, Physical Examination, and/or 12-Lead Electrocardiogram (ECG) Abnormalities
Physical Examination Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 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
|
0 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter AUC(0-t)
|
47.15 ng*hr/mL
Geometric Coefficient of Variation 17.98
|
47.83 ng*hr/mL
Geometric Coefficient of Variation 19.77
|
50.69 ng*hr/mL
Geometric Coefficient of Variation 17.74
|
51.37 ng*hr/mL
Geometric Coefficient of Variation 17.63
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter T1/2
|
6.45 hr
Standard Deviation 1.00
|
6.21 hr
Standard Deviation 1.25
|
5.86 hr
Standard Deviation 0.92
|
6.09 hr
Standard Deviation 0.94
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Tmax
|
1.38 hr
Standard Deviation 0.79
|
0.96 hr
Standard Deviation 0.61
|
1.94 hr
Standard Deviation 0.95
|
1.48 hr
Standard Deviation 0.58
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. AUC(0-t) is the area under the plasma concentration-time curve from time zero to time of last measurable concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Metformin PK Parameter AUC(0-t)
|
11826.52 ng*hr/mL
Geometric Coefficient of Variation 23.86
|
11875.08 ng*hr/mL
Geometric Coefficient of Variation 21.47
|
11796.60 ng*hr/mL
Geometric Coefficient of Variation 17.03
|
11681.05 ng*hr/mL
Geometric Coefficient of Variation 17.59
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study. One participant in period 3 (treatment D) was excluded from the pharmacokinetic analysis due to a predose concentration greater than 5% of Cmax.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. T 1/2 is the time required for the concentration of the drug to reach half of its original value in plasma.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=23 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=22 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Metformin PK Parameter T1/2
|
10.94 hr
Standard Deviation 4.13
|
13.15 hr
Standard Deviation 6.67
|
10.82 hr
Standard Deviation 3.18
|
11.13 hr
Standard Deviation 3.08
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Periods 1, 2, 3, & 4: pre-dosing, 15, 30, 45 mins & 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36 & 48 hrs post-dosingPopulation: All treated participants not discontinuing prior to the end of the study.
PK is the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body. Tmax is the time taken to reach the maximum observed plasma concentration.
Outcome measures
| Measure |
Treatment A
n=24 Participants
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 Participants
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 Participants
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 Participants
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Metformin PK Parameter Tmax
|
2.41 hr
Standard Deviation 0.78
|
2.54 hr
Standard Deviation 0.92
|
3.74 hr
Standard Deviation 0.54
|
3.74 hr
Standard Deviation 0.45
|
Adverse Events
Treatment A
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Treatment B
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Treatment C
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Treatment D
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 |
Treatment A
n=24 participants at risk
2.5 mg saxagliptin tablet + metformin 850 mg tablet single dose under fasted condition
|
Treatment B
n=24 participants at risk
Fixed dose combination (FDC) tablet (saxagliptin 2.5 mg + metformin 850 mg) single dose under fasted condition
|
Treatment C
n=23 participants at risk
2.5 mg saxagliptin tablet and metformin 850 mg tablet single dose under fed condition
|
Treatment D
n=23 participants at risk
FDC tablet (2.5 mg saxagliptin + metformin 850 mg) single dose under fed condition
|
|---|---|---|---|---|
|
Eye disorders
Vision blurred
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Nervous system disorders
Headache
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Nervous system disorders
Dizziness
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Nervous system disorders
Presyncope
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Gastrointestinal disorders
Nausea
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Gastrointestinal disorders
Diarrhoea
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
8.3%
2/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
13.0%
3/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Gastrointestinal disorders
Abdominal pain
|
8.3%
2/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Injury, poisoning and procedural complications
Muscle strain
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
Musculoskeletal and connective tissue disorders
Synovial cyst
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
General disorders
Fatigue
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.3%
1/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
4.2%
1/24 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
0.00%
0/23 • AEs: from study drug administration Day 1/Period 1 till study discharge. SAEs: from date of written consent until 30 days after discontinuation of dosing or study participation. Duration of the study was approximately 45 days (including screening).
|
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 of \<= 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 trail's primary publication.
- Publication restrictions are in place
Restriction type: OTHER