Trial Outcomes & Findings for Bioavailability of a Fixed Dose Combination Tablet With Empagliflozin (BI 10773) and Metformin Compared With the Monocomponents and Effect of Food on Bioavailability (NCT NCT01211197)
NCT ID: NCT01211197
Last Updated: 2015-08-21
Results Overview
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. Note the standard deviation is actually the coefficient of variation (CV).
COMPLETED
PHASE1
16 participants
1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administration
2015-08-21
Participant Flow
An open label, randomised, three-way crossover study. A washout period of at least 7 days was respected between drug administrations.
Participant milestones
| Measure |
FDC Fasted / Individual Tablets Fasted / FDC Fed
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin (BI 10773) and 1000mg metformin, under fasted conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
|
FDC Fasted / FDC Fed / Individual Tablets Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
|
Individual Tablets Fasted / FDC Fasted / FDC Fed
Patients received the three treatments in the following order:
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
|
Individual Tablets Fasted / FDC Fed / FDC Fasted
Patients received the three treatments in the following order:
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
|
FDC Fed / FDC Fasted / Individual Tablets Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
|
FDC Fed / Individual Tablets Fasted / FDC Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
|
|---|---|---|---|---|---|---|
|
Treatment Period 1 (1 Day)
STARTED
|
3
|
3
|
3
|
3
|
2
|
2
|
|
Treatment Period 1 (1 Day)
COMPLETED
|
3
|
3
|
3
|
3
|
2
|
2
|
|
Treatment Period 1 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 1 (7 Days)
STARTED
|
3
|
3
|
3
|
3
|
2
|
2
|
|
Washout Period 1 (7 Days)
COMPLETED
|
3
|
3
|
2
|
3
|
2
|
2
|
|
Washout Period 1 (7 Days)
NOT COMPLETED
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Treatment Period 2 (1 Day)
STARTED
|
3
|
3
|
2
|
3
|
2
|
2
|
|
Treatment Period 2 (1 Day)
COMPLETED
|
3
|
3
|
2
|
3
|
2
|
2
|
|
Treatment Period 2 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Washout Period 2 (7 Days)
STARTED
|
3
|
3
|
2
|
3
|
2
|
2
|
|
Washout Period 2 (7 Days)
COMPLETED
|
2
|
3
|
2
|
3
|
2
|
2
|
|
Washout Period 2 (7 Days)
NOT COMPLETED
|
1
|
0
|
0
|
0
|
0
|
0
|
|
Treatment Period 3 (1 Day)
STARTED
|
2
|
3
|
2
|
3
|
2
|
2
|
|
Treatment Period 3 (1 Day)
COMPLETED
|
2
|
3
|
2
|
3
|
2
|
2
|
|
Treatment Period 3 (1 Day)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
FDC Fasted / Individual Tablets Fasted / FDC Fed
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin (BI 10773) and 1000mg metformin, under fasted conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
|
FDC Fasted / FDC Fed / Individual Tablets Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
|
Individual Tablets Fasted / FDC Fasted / FDC Fed
Patients received the three treatments in the following order:
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
|
Individual Tablets Fasted / FDC Fed / FDC Fasted
Patients received the three treatments in the following order:
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
|
FDC Fed / FDC Fasted / Individual Tablets Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
|
FDC Fed / Individual Tablets Fasted / FDC Fasted
Patients received the three treatments in the following order:
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* FDC tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
|
|---|---|---|---|---|---|---|
|
Washout Period 1 (7 Days)
Withdrawal by Subject
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Washout Period 2 (7 Days)
Adverse Event
|
1
|
0
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Bioavailability of a Fixed Dose Combination Tablet With Empagliflozin (BI 10773) and Metformin Compared With the Monocomponents and Effect of Food on Bioavailability
Baseline characteristics by cohort
| Measure |
Study Overall
n=16 Participants
An open label, randomised, three-way crossover study. The three treatments administered were
* Fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions
* 12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions
* Fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions
A washout period of at least 7 days was respected between drug administrations.
|
|---|---|
|
Age, Continuous
|
35.8 years
STANDARD_DEVIATION 7.7 • n=93 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. Note the standard deviation is actually the coefficient of variation (CV).
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
|
2920 nmol*h/L
Standard Deviation 16.2
|
2860 nmol*h/L
Standard Deviation 18.5
|
2710 nmol*h/L
Standard Deviation 15.0
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Maximum measured concentration of empagliflozin (empa) in plasma. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Empa: Maximum Measured Concentration (Cmax)
|
404 nmol/L
Standard Deviation 17.4
|
405 nmol/L
Standard Deviation 15.8
|
259 nmol/L
Standard Deviation 20.3
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Area under the concentration-time curve of metformin in plasma over the time interval from 0 extrapolated to infinity. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)
|
10300 ng*h/mL
Standard Deviation 16.9
|
10100 ng*h/mL
Standard Deviation 21.2
|
10200 ng*h/mL
Standard Deviation 15.6
|
PRIMARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Maximum measured concentration of metformin in plasma. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Metformin: Maximum Measured Concentration (Cmax)
|
1550 ng/mL
Standard Deviation 19.1
|
1530 ng/mL
Standard Deviation 23.4
|
1180 ng/mL
Standard Deviation 25.5
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
|
2860 nmol*h/L
Standard Deviation 16.3
|
2800 nmol*h/L
Standard Deviation 18.6
|
2640 nmol*h/L
Standard Deviation 15.1
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Area under the concentration-time curve of metformin in plasma over the time interval from 0 to the time of the last quantifiable data point. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
|
9900 ng*h/mL
Standard Deviation 17.9
|
9720 ng*h/mL
Standard Deviation 22.3
|
9550 ng*h/mL
Standard Deviation 19.7
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Time from dosing to the maximum concentration of the analyte in plasma. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Time to Maximum Measured Concentration (Tmax)
Tmax of empagliflozin
|
1.50 hours
Full Range 34.2 • Interval 0.67 to 2.5
|
1.75 hours
Full Range 27.1 • Interval 1.0 to 2.5
|
3.00 hours
Full Range 54.6 • Interval 1.0 to 8.0
|
|
Time to Maximum Measured Concentration (Tmax)
Tmax of metformin
|
2.50 hours
Full Range 20.9 • Interval 2.0 to 4.0
|
2.50 hours
Full Range 26.3 • Interval 1.5 to 4.0
|
3.00 hours
Full Range 49.8 • Interval 1.5 to 8.0
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Terminal elimination rate constant in plasma. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Terminal Elimination Rate Constant in Plasma (λz)
λz of empagliflozin
|
0.0559 1/h
Standard Deviation 43.9
|
0.0601 1/h
Standard Deviation 53.2
|
0.0498 1/h
Standard Deviation 46.6
|
|
Terminal Elimination Rate Constant in Plasma (λz)
λz of metformin
|
0.0822 1/h
Standard Deviation 73.3
|
0.0756 1/h
Standard Deviation 82.7
|
0.0590 1/h
Standard Deviation 108
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Terminal half-life of the analyte in plasma. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Terminal Half-life in Plasma (T1/2)
T1/2 of empagliflozin
|
15.1 hours
Standard Deviation 46.6
|
16.0 hours
Standard Deviation 61.3
|
16.7 hours
Standard Deviation 43.0
|
|
Terminal Half-life in Plasma (T1/2)
T1/2 of metformin
|
16.6 hours
Standard Deviation 94.6
|
17.8 hours
Standard Deviation 76.9
|
30.5 hours
Standard Deviation 89.0
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Mean residence time of the analyte in the body after oral administration. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Mean Residence Time in the Body After Oral Administration (MRTpo)
MRTpo of empagliflozin
|
10.5 hours
Standard Deviation 17.6
|
10.9 hours
Standard Deviation 25.1
|
13.9 hours
Standard Deviation 23.0
|
|
Mean Residence Time in the Body After Oral Administration (MRTpo)
MRTpo of metformin
|
9.53 hours
Standard Deviation 52.0
|
10.2 hours
Standard Deviation 52.1
|
19.4 hours
Standard Deviation 101
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Apparent clearance of the analyte in the plasma after extravascular administration. Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Apparent Clearance After Extravascular Administration (CL/F)
CL/F of empagliflozin
|
162 mL/min
Standard Deviation 15.0
|
166 mL/min
Standard Deviation 17.1
|
174 mL/min
Standard Deviation 13.3
|
|
Apparent Clearance After Extravascular Administration (CL/F)
CL/F of metformin
|
1670 mL/min
Standard Deviation 20.2
|
1730 mL/min
Standard Deviation 25.4
|
1670 mL/min
Standard Deviation 18.8
|
SECONDARY outcome
Timeframe: 1 hour (h) before drug administration and 20 minutes (min), 40min, 1 h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 24h, 34h, 48h, 72h after drug administrationPopulation: Pharmacokinetic (PK) set included all evaluable subjects who took at least 1 dose of investigational medication, provided at least one observation for at least one primary PK endpoint without important protocol violations relevant to the evaluation of pharmacokinetics.
Apparent volume of distribution during the terminal phase (λz). Note the standard deviation is actually the CV.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Vz/F of metformin
|
2410 Litres
Standard Deviation 99.5
|
2650 Litres
Standard Deviation 86.0
|
4670 Litres
Standard Deviation 112
|
|
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Vz/F of empagliflozin
|
210 Litres
Standard Deviation 45.3
|
222 Litres
Standard Deviation 58.0
|
250 Litres
Standard Deviation 44.3
|
SECONDARY outcome
Timeframe: Drug administration up to 7 days after last drug administration, up to 8 daysPopulation: Treated set (TS) includes all subjects who took at least 1 dose of investigational medication and was used for safety analysis.
Clinically relevant abnormalities for physical examination, vital signs, ECG, blood chemistry and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as adverse events.
Outcome measures
| Measure |
FDC Fasted
n=15 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 Participants
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 Participants
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fed conditions.
|
|---|---|---|---|
|
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator.
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
FDC Fasted
Individual Tablets Fasted
FDC Fed
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
FDC Fasted
n=15 participants at risk
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
Individual Tablets Fasted
n=16 participants at risk
12.5mg empa and 1000mg metformin individual-component tablets under fasted conditions.
|
FDC Fed
n=14 participants at risk
A single fixed dose combination (FDC) tablet, containing 12.5mg empagliflozin and 1000mg metformin, under fasted conditions.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
18.8%
3/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
21.4%
3/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Infections and infestations
Rhinitis
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
6.2%
1/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Injury, poisoning and procedural complications
Wound
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
6.2%
1/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
6.2%
1/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Nervous system disorders
Headache
|
6.7%
1/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
6.2%
1/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
6.2%
1/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
0.00%
0/15 • Drug administration up to 7 days after last drug administration, up to 8 days
|
0.00%
0/16 • Drug administration up to 7 days after last drug administration, up to 8 days
|
7.1%
1/14 • Drug administration up to 7 days after last drug administration, up to 8 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place