Trial Outcomes & Findings for Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants (NCT NCT01068717)
NCT ID: NCT01068717
Last Updated: 2015-05-12
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
27 participants
Primary outcome timeframe
Days 1, 2, and 3 of Periods 1, 2, 3, and 4
Results posted on
2015-05-12
Participant Flow
A total of 27 participants were enrolled and randomly assigned to 1 of 4 treatment sequences: ADBC, BACD, CBDA, or DCAB. One participant withdrew from the study on Day -1 of Period 2 due to a family emergency and returned for early termination assessments on Day 4 of Period 2. She did not receive study drug in Period 2.
Participant milestones
| Measure |
Treatment Schedule ADBC
(Treatment A) A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state.
|
Treatment Schedule BACD
(Treatment B) A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state.
|
Treatment Schedule CBDA
(Treatment C) A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fed state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state.
|
Treatment Schedule DCAB
(Treatment D) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state.
|
|---|---|---|---|---|
|
Period 1: Treatment Schedule Phase 1
STARTED
|
7
|
6
|
7
|
7
|
|
Period 1: Treatment Schedule Phase 1
COMPLETED
|
6
|
6
|
7
|
7
|
|
Period 1: Treatment Schedule Phase 1
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Period 2: Treatment Schedule Phase 2
STARTED
|
6
|
6
|
7
|
7
|
|
Period 2: Treatment Schedule Phase 2
COMPLETED
|
6
|
6
|
7
|
7
|
|
Period 2: Treatment Schedule Phase 2
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 3: Treatment Schedule Phase 3
STARTED
|
7
|
6
|
7
|
7
|
|
Period 3: Treatment Schedule Phase 3
COMPLETED
|
7
|
6
|
7
|
7
|
|
Period 3: Treatment Schedule Phase 3
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Period 4: Treatment Schedule Phase 4
STARTED
|
7
|
6
|
7
|
7
|
|
Period 4: Treatment Schedule Phase 4
COMPLETED
|
7
|
6
|
7
|
7
|
|
Period 4: Treatment Schedule Phase 4
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Treatment Schedule ADBC
(Treatment A) A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state.
|
Treatment Schedule BACD
(Treatment B) A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state.
|
Treatment Schedule CBDA
(Treatment C) A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the fed state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment D) a single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state.
|
Treatment Schedule DCAB
(Treatment D) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment C) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fed state. Then, (Treatment A) a single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period. Then, (Treatment B) a single oral dose of 2.5-mg saxagliptin/500- mg metformin FDC administered in the fasted state.
|
|---|---|---|---|---|
|
Period 1: Treatment Schedule Phase 1
Patient withdrew; returned for period 3
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants
Baseline characteristics by cohort
| Measure |
All Treated
n=27 Participants
All participants who received study medication.
|
|---|---|
|
Age, Customized
|
32 Years
n=5 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
8 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black or African American
|
5 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
22 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Observed Maximum Plasma Concentration (Cmax) of Saxagliptin, Tablets and Fixed-dose Combination (FDC), Administered to Participants in the Fasted and Fed States
|
10.54 ng/mL
Geometric Coefficient of Variation 26
|
11.53 ng/mL
Geometric Coefficient of Variation 26
|
12.71 ng/mL
Geometric Coefficient of Variation 36
|
12.79 ng/mL
Geometric Coefficient of Variation 37
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Observed Cmax of Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
|
1058.19 ng/mL
Geometric Coefficient of Variation 23
|
1044.70 ng/mL
Geometric Coefficient of Variation 25
|
810.08 ng/mL
Geometric Coefficient of Variation 22
|
811.94 ng/mL
Geometric Coefficient of Variation 20
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=25 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
t1/2 saxagliptin
|
6.16 Hours
Standard Deviation 1.06
|
6.69 Hours
Standard Deviation 0.90
|
5.99 Hours
Standard Deviation 0.91
|
6.15 Hours
Standard Deviation 0.79
|
|
Terminal Half-life (t1/2) of Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
t1/2 metformin
|
11.05 Hours
Standard Deviation 3.94
|
13.02 Hours
Standard Deviation 5.37
|
10.72 Hours
Standard Deviation 2.61
|
10.96 Hours
Standard Deviation 4.03
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-time Curve From Time 0 to the Last Quantifiable Concentration (AUC[0-t]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States
|
50.28 ng*h/mL
Geometric Coefficient of Variation 24
|
51.60 ng*h/mL
Geometric Coefficient of Variation 23
|
59.00 ng*h/mL
Geometric Coefficient of Variation 20
|
58.94 ng*h/mL
Geometric Coefficient of Variation 19
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
AUC[0-t] for Metformin, Tablets and FDC, Given in the Fasted and Fed States
|
8035.25 ng*h/mL
Geometric Coefficient of Variation 22
|
7906.00 ng*h/mL
Geometric Coefficient of Variation 21
|
7497.56 ng*h/mL
Geometric Coefficient of Variation 23
|
7654.00 ng*h/mL
Geometric Coefficient of Variation 19
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=26 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=25 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=25 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
AUC From Time 0 Extrapolated to Infinity (AUC[0-inf]) for Saxagliptin, Tablets and FDC, Given in the Fasted and Fed States
|
52.17 ng*h/mL
Geometric Coefficient of Variation 24
|
53.73 ng*h/mL
Geometric Coefficient of Variation 23
|
61.31 ng*h/mL
Geometric Coefficient of Variation 20
|
60.88 ng*h/mL
Geometric Coefficient of Variation 20
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=26 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=25 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=25 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
AUC[0-inf] for Metformin, Tablets and FDC, Administered in the Fasted and Fed States
|
8142.68 ng*h/mL
Geometric Coefficient of Variation 22
|
8070.25 ng*h/mL
Geometric Coefficient of Variation 20
|
7612.94 ng*h/mL
Geometric Coefficient of Variation 24
|
7690.69 ng*h/mL
Geometric Coefficient of Variation 18
|
PRIMARY outcome
Timeframe: Days 1, 2, and 3 of Periods 1, 2, 3, and 4Population: All participants who received at least 1 of the 4 treatments and had sufficient plasma concentration data to facilitate the calculation of at least 1 primary pharmacokinetic parameter for at least 1 of the treatments.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
Tmax saxagliptin
|
1.00 Hours
Interval 0.25 to 3.0
|
0.75 Hours
Interval 0.3 to 4.0
|
1.50 Hours
Interval 0.5 to 8.0
|
1.00 Hours
Interval 0.5 to 3.0
|
|
Time to Achieve the Observed Maximum Plasma Concentration (Tmax) for Saxagliptin and Metformin, Tablets and FDC, Administered to Participants in the Fasted and Fed States
Tmax metformin
|
3.00 Hours
Interval 0.5 to 4.0
|
3.00 Hours
Interval 1.0 to 6.0
|
4.00 Hours
Interval 2.0 to 6.0
|
4.00 Hours
Interval 1.5 to 8.0
|
SECONDARY outcome
Timeframe: Continuously over Days 1 to 3 of treatment Periods 1, 2, 3, and 4Population: All enrolled participants who received study medication.
An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation
Death
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation
Serious Adverse Events
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Death as Outcome, Serious Adverse Events, and Adverse Events (AEs) Leading to Discontinuation
AEs Leading to Discontinuation
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At screening visit, at Day -1 of Periods 1 through 4, and at dischargePopulation: All enrolled participants who received study medication.
Clinically significant was determined by the investigator. Hematology tests included hemoglobin, hematocrit, red blood cell count, total leukocyte count (including differential), and platelet count. Serum chemistry tests included aspartate aminotransferase, alanine aminotransferase, total bilirubin, alkaline phosphatase, lactate dehydrogenase, creatinine, blood urea nitrogen, uric acid, fasting glucose, total protein, albumin, sodium, potassium, chloride, calcium, phosphorus, and creatine kinase. Urinalysis included protein, glucose, blood, leukocyte esterase, specific gravity, and pH.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results
Hematology test results
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results
Serum chemistry test results
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Clinically Significant Abnormalities in Hematology, Serum Chemistry, and Urinalysis Laboratory Test Results
Urinalysis results
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At screening visit, Day -1 of Period 1, and at study dischargePopulation: All enrolled participants who received study medication.
Clinically significant was determined by the investigator. ECGs were recorded after participants had been supine for at least 5 minutes.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Results
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: At screening visit, prior to dosing on Day 1 of Periods 1 through 4, and at study discharge.Population: All enrolled participants who received study medication.
Clinically significant was determined by the investigator. Blood pressure and heart rate were measured after the participant had been seated quietly for at least 5 minutes.
Outcome measures
| Measure |
Treatment A: Saxagliptin and Metformin Tablets, Fasted
n=27 Participants
A single oral dose of saxagliptin, 2.5-mg and metformin 500-mg tablets administered together in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment B: Saxagliptin and Metformin FDC, Fasted
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin fixed-dose combination (FDC) administered in the fasted state, followed by a 7-day (minimum) washout period.
|
Treatment C: Saxagliptin and Metformin Tablets, Fed
n=26 Participants
A single oral dose of saxagliptin 2.5-mg and metformin 500-mg tablets administered together in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
Treatment D: Saxagliptin and Metformin FDC, Fed
n=26 Participants
A single oral dose of 2.5-mg saxagliptin/500-mg metformin FDC administered in the morning within 5 minutes of completing a standard high-fat, high-calorie breakfast (fed state), followed by a 7-day (minimum) washout period.
|
|---|---|---|---|---|
|
Number of Participants With Clinically Significant Abnormalities in Body Temperature, Blood Pressure, or Heart Rate
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Fasted: 2.5mg Onglyza + 500mg Glucophage
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Fasted: 2.5mg Saxa/500mg Metformin FDC
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Fed: 2.5mg Onglyza + 500mg Glucophage
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Fed: 2.5mg Saxa/500mg Metformin FDC
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 |
Fasted: 2.5mg Onglyza + 500mg Glucophage
n=27 participants at risk
|
Fasted: 2.5mg Saxa/500mg Metformin FDC
n=26 participants at risk
|
Fed: 2.5mg Onglyza + 500mg Glucophage
n=26 participants at risk
|
Fed: 2.5mg Saxa/500mg Metformin FDC
n=26 participants at risk
|
|---|---|---|---|---|
|
Eye disorders
Asthenopia
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/26
|
|
Psychiatric disorders
Abnormal dreams
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/26
|
|
Nervous system disorders
Headache
|
0.00%
0/27
|
0.00%
0/26
|
7.7%
2/26
|
0.00%
0/26
|
|
Gastrointestinal disorders
Nausea
|
3.7%
1/27
|
0.00%
0/26
|
7.7%
2/26
|
3.8%
1/26
|
|
Gastrointestinal disorders
Vomiting
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/26
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/27
|
0.00%
0/26
|
11.5%
3/26
|
0.00%
0/26
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
3.8%
1/26
|
|
Gastrointestinal disorders
Eructation
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
3.8%
1/26
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/26
|
3.8%
1/26
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/26
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
3.8%
1/26
|
|
Gastrointestinal disorders
Bowel movement irregularity
|
0.00%
0/27
|
3.8%
1/26
|
0.00%
0/26
|
0.00%
0/26
|
|
Skin and subcutaneous tissue disorders
Hidradenitis
|
3.7%
1/27
|
0.00%
0/26
|
0.00%
0/26
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/27
|
0.00%
0/26
|
0.00%
0/26
|
3.8%
1/26
|
|
General disorders
Vessel puncture site pain
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/26
|
|
General disorders
Venipuncture site inflammation
|
0.00%
0/27
|
0.00%
0/26
|
3.8%
1/26
|
0.00%
0/26
|
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