Trial Outcomes & Findings for Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (B) (NCT NCT00897390)
NCT ID: NCT00897390
Last Updated: 2015-05-21
Results Overview
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
24 participants
Primary outcome timeframe
pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each period
Results posted on
2015-05-21
Participant Flow
58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).
Participant milestones
| Measure |
All Treated Participants
Participants were assigned to 1 of 4 treatment sequences (A-D-B-C, B-A-C-D, C-B-D-A, D-C-A-B). Treatment A=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fasted; Treatment B=fixed-dose combination (FDC) tablet of 2.5-mg saxagliptin/1000-mg metformin immediate release (IR), fasted; Treatment C=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fed; Treatment D=FDC tablet of 2.5-mg saxagliptin/1000-mg metformin IR, fed. The washout between each dose was at least 7 days.
|
|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
18
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
All Treated Participants
Participants were assigned to 1 of 4 treatment sequences (A-D-B-C, B-A-C-D, C-B-D-A, D-C-A-B). Treatment A=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fasted; Treatment B=fixed-dose combination (FDC) tablet of 2.5-mg saxagliptin/1000-mg metformin immediate release (IR), fasted; Treatment C=2.5-mg saxagliptin tablet co-administered with 1000-mg metformin IR tablet, fed; Treatment D=FDC tablet of 2.5-mg saxagliptin/1000-mg metformin IR, fed. The washout between each dose was at least 7 days.
|
|---|---|
|
Overall Study
Adverse Event
|
2
|
|
Overall Study
No Longer Met Study Criteria
|
1
|
|
Overall Study
Personal Reasons
|
1
|
|
Overall Study
Did not Return for the Clinic Visit
|
2
|
Baseline Characteristics
Bioequivalence Study of Saxagliptin and Glucophage Combination Formulations in Healthy Subjects (B)
Baseline characteristics by cohort
| Measure |
All Enrolled and Treated Participants
n=24 Participants
|
|---|---|
|
Age, Continuous
|
30 years
STANDARD_DEVIATION 6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
20 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black
|
4 participants
n=5 Participants
|
|
Body Mass Index
|
26.5 kg/m^2
STANDARD_DEVIATION 3.8 • n=5 Participants
|
|
weight
|
79.9 kg
STANDARD_DEVIATION 15.0 • n=5 Participants
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Saxagliptin Pharmacokinetic (PK) Parameter Area Under the Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinite Time (AUC[INF])
|
47.25 ng*h/mL
Interval 30.6 to 66.0
|
48.91 ng*h/mL
Interval 28.7 to 80.7
|
52.89 ng*h/mL
Interval 37.4 to 75.1
|
51.11 ng*h/mL
Interval 34.2 to 73.7
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Plasma Concentration (AUC[0-T])
|
44.90 ng*h/mL
Interval 29.1 to 64.3
|
46.57 ng*h/mL
Interval 27.8 to 77.7
|
50.50 ng*h/mL
Interval 35.6 to 73.2
|
49.09 ng*h/mL
Interval 33.5 to 71.3
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Maximum Observed Plasma Concentration (Cmax)
|
8.58 ng/mL
Interval 5.2 to 15.5
|
9.09 ng/mL
Interval 5.5 to 17.1
|
10.97 ng/mL
Interval 7.6 to 18.2
|
10.80 ng/mL
Interval 7.4 to 15.9
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Plasma Terminal Half-life (T-HALF)
|
6.66 hours
Standard Deviation 1.185
|
6.34 hours
Standard Deviation 0.941
|
6.47 hours
Standard Deviation 1.529
|
5.78 hours
Standard Deviation 1.333
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of saxagliptin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Saxagliptin PK Parameter Time of Maximum Observed Plasma Concentration (Tmax)
|
1.50 hours
Interval 0.5 to 4.0
|
0.75 hours
Interval 0.3 to 3.0
|
1.00 hours
Interval 0.3 to 3.0
|
1.50 hours
Interval 0.3 to 3.0
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Metformin PK Parameter AUC(INF)
|
13363.46 ng*h/mL
Interval 8872.9 to 19164.2
|
12677.92 ng*h/mL
Interval 8827.3 to 16811.6
|
12357.87 ng*h/mL
Interval 6875.3 to 15926.2
|
12126.19 ng*h/mL
Interval 7328.6 to 15424.7
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Metformin PK Parameter AUC(0-T)
|
13238.43 ng*h/mL
Interval 8782.0 to 18991.8
|
12400.41 ng*h/mL
Interval 8105.3 to 16603.8
|
12124.31 ng*h/mL
Interval 6629.2 to 15842.4
|
11996.88 ng*h/mL
Interval 7142.5 to 15326.6
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Metformin PK Parameter Cmax
|
2004.99 ng/mL
Interval 1187.2 to 3144.6
|
1830.76 ng/mL
Interval 1142.5 to 2662.5
|
1666.55 ng/mL
Interval 768.7 to 2256.5
|
1642.90 ng/mL
Interval 848.1 to 2018.3
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Metformin PK Parameter T-HALF
|
8.43 hours
Standard Deviation 2.956
|
10.58 hours
Standard Deviation 8.895
|
11.78 hours
Standard Deviation 5.999
|
7.63 hours
Standard Deviation 2.309
|
PRIMARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of metformin were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Metformin PK Parameter Tmax
|
2.00 hours
Interval 1.0 to 4.0
|
2.98 hours
Interval 1.5 to 4.0
|
4.00 hours
Interval 2.0 to 4.0
|
4.00 hours
Interval 3.0 to 4.0
|
SECONDARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
BMS-510849 PK Parameter AUC(INF)
|
118.54 ng*h/mL
Interval 58.7 to 174.4
|
116.19 ng*h/mL
Interval 48.5 to 212.4
|
127.67 ng*h/mL
Interval 62.5 to 217.8
|
127.25 ng*h/mL
Interval 59.4 to 219.3
|
SECONDARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
BMS-510849 PK Parameter AUC(0-T)
|
108.31 ng*h/mL
Interval 52.0 to 169.2
|
106.11 ng*h/mL
Interval 42.3 to 201.4
|
117.42 ng*h/mL
Interval 54.3 to 210.7
|
117.43 ng*h/mL
Interval 51.1 to 210.9
|
SECONDARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
BMS-510849 PK Parameter Cmax
|
16.77 ng/mL
Interval 6.4 to 32.8
|
15.17 ng/mL
Interval 4.7 to 32.0
|
18.24 ng/mL
Interval 7.6 to 36.5
|
18.58 ng/mL
Interval 6.2 to 33.5
|
SECONDARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from their respective plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
BMS-510849 PK Parameter T-Half
|
8.05 hours
Standard Deviation 1.427
|
7.31 hours
Standard Deviation 1.369
|
7.48 hours
Standard Deviation 1.504
|
7.35 hours
Standard Deviation 1.622
|
SECONDARY outcome
Timeframe: pre-dose, post-dose at 15, 30, 45, 90 minutes, hours 1, 2, 3, 4, 6, 8, 12, 18, 24, 36 and 48 of each periodPopulation: Treated participants with PK measures
Single-dose PK parameters of the active metabolite of saxagliptin, BMS-510849, were derived from plasma concentration versus time data.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
BMS-510849 PK Parameter T-Max
|
2.00 hours
Interval 1.0 to 4.0
|
2.00 hours
Interval 0.8 to 4.0
|
2.00 hours
Interval 1.0 to 4.0
|
2.00 hours
Interval 1.0 to 4.0
|
SECONDARY outcome
Timeframe: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days). SAEs collected from date of written consent until 30 days post discontinuation of dosing or subject's participation in the study.Population: All treated participants
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a patient or clinical investigation subject administered an investigational (medicinal) product and that does not necessarily have a causal relationship with this treatment. An SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
Deaths
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
SAEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
AEs
|
5 participants
|
2 participants
|
4 participants
|
3 participants
|
|
Deaths, Serious Adverse Events (SAEs), Adverse Events (AEs), and Discontinuations Due to AEs
Discontinuations dues to AEs
|
0 participants
|
0 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: AEs collected from Day 1/Period 1 through study discharge (study duration: approximately 45 days).Population: All treated participants
See Outcome Measure 16 for a definition of AEs. AEs of clinical interest for saxagliptin were defined as those relating to the following:skin disorders, infection-related AEs (system organ class \[SOC\]: Infections and Infestations), thrombocytopenia, lymphopenia, hypoglycemia, cardiovascular AEs indicative of acute cardiovascular events, localized edema, fractures, pancreatitis, and AEs of hypersensitivity.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=22 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
AEs of Special Interest
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.Population: Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.
Laboratory abnormalities=any result that is clinically significant, met the definition of an SAE, required discontinuation or interruption of study drug, or required specific corrective therapy. Upper normal (UN)/lower normal (LN) values: leukocytes UN, 11.40x10\^3 c/uL; absolute neutrophils/bands LN, 1.500x10\^3 c/uL; aspartate aminotransferase UN, 48 U/L; alanine aminotransferase UN, 67 U/L; blood urea nitrogen UN, 20.0 mg/dL; creatine kinase UN, 350 U/L; lactate dehydrogenase UN, 249 U/L.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=20 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=21 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Leukocytes - High(>1.2 * upper limit normal [ULN])
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Abs. Neutrophils/Bands-Low (<=lower LN [LLN])
|
1 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Aspartate Aminotransferase - High (>1.25 * ULN)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Alanine Aminotransferase - High (>1.25 * ULN)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Blood Urea Nitrogen - High (1.1 * ULN)
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Creatine Kinase - High (>1.5 ULN)
|
1 participants
|
1 participants
|
0 participants
|
2 participants
|
|
Number of Participants With Marked Laboratory Abnormalities (MA)
Lactate Dehydrogenase - High (>1.25 ULN)
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Within 21 days of study Day 1, Days 1-3 of Periods 1, 2, 3, and 4.Population: Number of Participants Analyzed=treated participants; n=number of participants evaluated for this measure (among the 6 participants who had the urinary WBC and RBC test, there are only 2 had a pre-study evaluation, and were therefore evaluable for these measures.
Protein, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Glucose, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). Blood, Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 1+, then \>= 2 \* pretreatment). White Blood Cell (WBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). Red Blood Cell (RBC), Urine Abnormality: if value \>= 2+ (or if pretreatment value \>= 2+, then \>= 4+). (The '+' is a normal lab result and refers to the magnitude of the finding.)
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=20 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=21 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Number of Participants With Marked Urinalysis Abnormalities
Protein, Urine (n=19, 19, 20, 21)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Urinalysis Abnormalities
Glucose, Urine (n=19, 19, 20, 21)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Marked Urinalysis Abnormalities
Blood, Urine (n=19, 19, 20, 21)
|
1 participants
|
0 participants
|
0 participants
|
2 participants
|
|
Number of Participants With Marked Urinalysis Abnormalities
White Blood Cells, Urine (n=2, 2, 2, 2)
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Marked Urinalysis Abnormalities
Red Blood Cells, Urine (n=2, 2, 2, 2)
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: At Screening (within 21 days of Study Day 1), Day -1 of Period 1 (ECG and Physical only), Day 1 of Periods 1-4 (Vitals only), at Study Discharge (Day 3 of Period 4) or DiscontinuationPopulation: Treated participants. One participant each in Arm C and Arm D was not evaluated for this measure.
12-lead Electrocardiogram (ECG), Vital Sign (body temperature, respiratory rate, seated blood pressure and heart rate), and Physical Finding Abnormalities reported by investigator as AEs.
Outcome measures
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 Participants
Single oral dose of a fixed dose combination (FDC) tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=20 Participants
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=21 Participants
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal
|
|---|---|---|---|---|
|
Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
ECG Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
Vital Sign Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Electrocardiogram (ECG), Vital Sign, and Physical Finding Abnormalities
Physical Finding Abnormalities
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Not Dosed
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fasted
n=19 participants at risk
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fasted conditions.
|
FDC Tablet 2.5-mg Saxa/1000-mg Met Tablet, Fasted
n=19 participants at risk
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fasted conditions
|
2.5-mg Saxa Tablet/1000-mg Met Tablet, Fed
n=21 participants at risk
Co-administration of single oral doses of a 2.5 mg tablet of saxagliptin and a 1000 mg tablet of metformin IR under fed conditions with a standard meal.
|
FDC Tablet of 2.5-mg Saxa/1000-mg Met Tablet, Fed
n=24 participants at risk
Single oral dose of a FDC tablet consisting of 2.5 mg saxagliptin/ 1000 mg metformin IR under fed conditions with a standard meal.
|
Not Dosed
n=34 participants at risk
58 participants were enrolled in the study; 34 participants were not dosed (23 no longer met study criteria, 4 withdrew consent, and 7 for other reasons).
|
|---|---|---|---|---|---|
|
Eye disorders
EYE DISCHARGE
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Investigations
ALANINE AMINOTRANSFERASE INCREASED
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Investigations
BLOOD LACTATE DEHYDROGENASE INCREASED
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Investigations
BLOOD CREATINE PHOSPHOKINASE INCREASED
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Cardiac disorders
PALPITATIONS
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Nervous system disorders
HEADACHE
|
16.7%
1/6
|
33.3%
2/6
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/34
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
NAUSEA
|
16.7%
1/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
VOMITING
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
DIARRHOEA
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
33.3%
2/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
DYSPEPSIA
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
FLATULENCE
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
CONSTIPATION
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/34
|
|
Ear and labyrinth disorders
EAR PAIN
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/34
|
|
Ear and labyrinth disorders
EAR DISCOMFORT
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Reproductive system and breast disorders
MENSTRUATION DELAYED
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Musculoskeletal and connective tissue disorders
PAIN IN JAW
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
COUGH
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
RHINORRHOEA
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
SINUS CONGESTION
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
THROAT IRRITATION
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/34
|
|
Respiratory, thoracic and mediastinal disorders
OROPHARYNGEAL PAIN
|
0.00%
0/6
|
0.00%
0/6
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/34
|
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