Diabetes Mellitus, Type 2
Conditions
Brief summary
The objective of the current study is to determine the relative bioavailability of a BI 10773 / metformin fixed dose combination tablet compared to single tablets of BI 10773 and metformin when administered together and to assess the effect of food on the bioavailability the fixed dose combination tablet
Interventions
DRUGC: BI 10773 / metformin tablet
BI 10773 / metformin fixed dose combination tablet after a high fat, high caloric meal
DRUGB: BI 10773 tablet and metformin tablet
BI 10773 and metformin single tablets, administered together in fasted state
DRUGA: BI 10773 / metformin tablet
BI 10773 / metformin fixed dose combination tablet in fasted state
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males and females according to the following criteria 2. Body Mass Index 18.5 to 29.9 kg/m2 (incl.)
Exclusion criteria
1. Any finding of the medical examination (including Blood Pressure, Pulse Rate and electrocardiogram) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 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 | 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). |
| Empa: Maximum Measured Concentration (Cmax) | 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 | Maximum measured concentration of empagliflozin (empa) in plasma. Note the standard deviation is actually the CV. |
| Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 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 | 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. |
| Metformin: Maximum Measured Concentration (Cmax) | 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 | Maximum measured concentration of metformin in plasma. Note the standard deviation is actually the CV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Half-life in Plasma (T1/2) | 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 | Terminal half-life of the analyte in plasma. Note the standard deviation is actually the CV. |
| Mean Residence Time in the Body After Oral Administration (MRTpo) | 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 | Mean residence time of the analyte in the body after oral administration. Note the standard deviation is actually the CV. |
| Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 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 | 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. |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 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 | Apparent volume of distribution during the terminal phase (λz). Note the standard deviation is actually the CV. |
| Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. | Drug administration up to 7 days after last drug administration, up to 8 days | 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. |
| Apparent Clearance After Extravascular Administration (CL/F) | 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 | Apparent clearance of the analyte in the plasma after extravascular administration. Note the standard deviation is actually the CV. |
| Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 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 | 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. |
| Time to Maximum Measured Concentration (Tmax) | 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 | Time from dosing to the maximum concentration of the analyte in plasma. Note the standard deviation is actually the CV. |
| Terminal Elimination Rate Constant in Plasma (λz) | 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 | Terminal elimination rate constant in plasma. Note the standard deviation is actually the CV. |
Countries
Germany
Participant flow
Pre-assignment details
An open label, randomised, three-way crossover study. A washout period of at least 7 days was respected between drug administrations.
Participants by arm
| Arm | Count |
|---|---|
| Study Overall 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. | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| 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
| Characteristic | Study Overall |
|---|---|
| Age, Continuous | 35.8 years STANDARD_DEVIATION 7.7 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 15 | 6 / 16 | 8 / 14 |
| serious Total, serious adverse events | 0 / 15 | 0 / 16 | 0 / 14 |
Outcome results
Primary
Empa: Area Under the Curve 0 to Infinity (AUC0-∞)
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).
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 2920 nmol*h/L | Standard Deviation 16.2 |
| Individual Tablets Fasted | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 2860 nmol*h/L | Standard Deviation 18.5 |
| FDC Fed | Empa: Area Under the Curve 0 to Infinity (AUC0-∞) | 2710 nmol*h/L | Standard Deviation 15 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted.90% CI: [95.75, 105.67]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [89.85, 100.33]ANOVA
Primary
Empa: Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagliflozin (empa) in plasma. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Empa: Maximum Measured Concentration (Cmax) | 404 nmol/L | Standard Deviation 17.4 |
| Individual Tablets Fasted | Empa: Maximum Measured Concentration (Cmax) | 405 nmol/L | Standard Deviation 15.8 |
| FDC Fed | Empa: Maximum Measured Concentration (Cmax) | 259 nmol/L | Standard Deviation 20.3 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted90% CI: [91.76, 107.49]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [55.97, 73.87]ANOVA
Primary
Metformin: Area Under the Curve 0 to Infinity (AUC0-∞)
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 10300 ng*h/mL | Standard Deviation 16.9 |
| Individual Tablets Fasted | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 10100 ng*h/mL | Standard Deviation 21.2 |
| FDC Fed | Metformin: Area Under the Curve 0 to Infinity (AUC0-∞) | 10200 ng*h/mL | Standard Deviation 15.6 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted90% CI: [93.87, 111.15]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [91.7, 110.51]ANOVA
Primary
Metformin: Maximum Measured Concentration (Cmax)
Maximum measured concentration of metformin in plasma. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Metformin: Maximum Measured Concentration (Cmax) | 1550 ng/mL | Standard Deviation 19.1 |
| Individual Tablets Fasted | Metformin: Maximum Measured Concentration (Cmax) | 1530 ng/mL | Standard Deviation 23.4 |
| FDC Fed | Metformin: Maximum Measured Concentration (Cmax) | 1180 ng/mL | Standard Deviation 25.5 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted90% CI: [95.3, 112.39]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [63.68, 88.64]ANOVA
Secondary
Apparent Clearance After Extravascular Administration (CL/F)
Apparent clearance of the analyte in the plasma after extravascular administration. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of empagliflozin | 162 mL/min | Standard Deviation 15 |
| FDC Fasted | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of metformin | 1670 mL/min | Standard Deviation 20.2 |
| Individual Tablets Fasted | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of empagliflozin | 166 mL/min | Standard Deviation 17.1 |
| Individual Tablets Fasted | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of metformin | 1730 mL/min | Standard Deviation 25.4 |
| FDC Fed | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of empagliflozin | 174 mL/min | Standard Deviation 13.3 |
| FDC Fed | Apparent Clearance After Extravascular Administration (CL/F) | CL/F of metformin | 1670 mL/min | Standard Deviation 18.8 |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Apparent volume of distribution during the terminal phase (λz). Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of empagliflozin | 210 Litres | Standard Deviation 45.3 |
| FDC Fasted | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of metformin | 2410 Litres | Standard Deviation 99.5 |
| Individual Tablets Fasted | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of empagliflozin | 222 Litres | Standard Deviation 58 |
| Individual Tablets Fasted | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of metformin | 2650 Litres | Standard Deviation 86 |
| FDC Fed | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of empagliflozin | 250 Litres | Standard Deviation 44.3 |
| FDC Fed | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Vz/F of metformin | 4670 Litres | Standard Deviation 112 |
Secondary
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator.
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.
Time frame: Drug administration up to 7 days after last drug administration, up to 8 days
Population: Treated set (TS) includes all subjects who took at least 1 dose of investigational medication and was used for safety analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| FDC Fasted | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. | 0 participants |
| Individual Tablets Fasted | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. | 0 participants |
| FDC Fed | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Blood Chemistry and Assessment of Tolerability by the Investigator. | 0 participants |
Secondary
Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 2860 nmol*h/L | Standard Deviation 16.3 |
| Individual Tablets Fasted | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 2800 nmol*h/L | Standard Deviation 18.6 |
| FDC Fed | Empa: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 2640 nmol*h/L | Standard Deviation 15.1 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted90% CI: [96.03, 106.11]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [89.22, 99.87]ANOVA
Secondary
Mean Residence Time in the Body After Oral Administration (MRTpo)
Mean residence time of the analyte in the body after oral administration. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of empagliflozin | 10.5 hours | Standard Deviation 17.6 |
| FDC Fasted | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of metformin | 9.53 hours | Standard Deviation 52 |
| Individual Tablets Fasted | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of empagliflozin | 10.9 hours | Standard Deviation 25.1 |
| Individual Tablets Fasted | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of metformin | 10.2 hours | Standard Deviation 52.1 |
| FDC Fed | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of empagliflozin | 13.9 hours | Standard Deviation 23 |
| FDC Fed | Mean Residence Time in the Body After Oral Administration (MRTpo) | MRTpo of metformin | 19.4 hours | Standard Deviation 101 |
Secondary
Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz)
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.
Time frame: 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
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FDC Fasted | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 9900 ng*h/mL | Standard Deviation 17.9 |
| Individual Tablets Fasted | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 9720 ng*h/mL | Standard Deviation 22.3 |
| FDC Fed | Metformin: Area Under the Curve 0 to the Last Quantifiable Data Point (AUC0-tz) | 9550 ng*h/mL | Standard Deviation 19.7 |
Comparison: Ratio calculated as FDC fasted divided by individual tablets fasted90% CI: [95.59, 111.25]ANOVA
Comparison: Ratio calculated as FDC fed divided by FDC fasted90% CI: [87.23, 107.78]ANOVA
Secondary
Terminal Elimination Rate Constant in Plasma (λz)
Terminal elimination rate constant in plasma. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Terminal Elimination Rate Constant in Plasma (λz) | λz of empagliflozin | 0.0559 1/h | Standard Deviation 43.9 |
| FDC Fasted | Terminal Elimination Rate Constant in Plasma (λz) | λz of metformin | 0.0822 1/h | Standard Deviation 73.3 |
| Individual Tablets Fasted | Terminal Elimination Rate Constant in Plasma (λz) | λz of empagliflozin | 0.0601 1/h | Standard Deviation 53.2 |
| Individual Tablets Fasted | Terminal Elimination Rate Constant in Plasma (λz) | λz of metformin | 0.0756 1/h | Standard Deviation 82.7 |
| FDC Fed | Terminal Elimination Rate Constant in Plasma (λz) | λz of empagliflozin | 0.0498 1/h | Standard Deviation 46.6 |
| FDC Fed | Terminal Elimination Rate Constant in Plasma (λz) | λz of metformin | 0.0590 1/h | Standard Deviation 108 |
Secondary
Terminal Half-life in Plasma (T1/2)
Terminal half-life of the analyte in plasma. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Terminal Half-life in Plasma (T1/2) | T1/2 of empagliflozin | 15.1 hours | Standard Deviation 46.6 |
| FDC Fasted | Terminal Half-life in Plasma (T1/2) | T1/2 of metformin | 16.6 hours | Standard Deviation 94.6 |
| Individual Tablets Fasted | Terminal Half-life in Plasma (T1/2) | T1/2 of empagliflozin | 16.0 hours | Standard Deviation 61.3 |
| Individual Tablets Fasted | Terminal Half-life in Plasma (T1/2) | T1/2 of metformin | 17.8 hours | Standard Deviation 76.9 |
| FDC Fed | Terminal Half-life in Plasma (T1/2) | T1/2 of empagliflozin | 16.7 hours | Standard Deviation 43 |
| FDC Fed | Terminal Half-life in Plasma (T1/2) | T1/2 of metformin | 30.5 hours | Standard Deviation 89 |
Secondary
Time to Maximum Measured Concentration (Tmax)
Time from dosing to the maximum concentration of the analyte in plasma. Note the standard deviation is actually the CV.
Time frame: 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
Population: 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.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| FDC Fasted | Time to Maximum Measured Concentration (Tmax) | Tmax of empagliflozin | 1.50 hours | Full Range 34.2 |
| FDC Fasted | Time to Maximum Measured Concentration (Tmax) | Tmax of metformin | 2.50 hours | Full Range 20.9 |
| Individual Tablets Fasted | Time to Maximum Measured Concentration (Tmax) | Tmax of empagliflozin | 1.75 hours | Full Range 27.1 |
| Individual Tablets Fasted | Time to Maximum Measured Concentration (Tmax) | Tmax of metformin | 2.50 hours | Full Range 26.3 |
| FDC Fed | Time to Maximum Measured Concentration (Tmax) | Tmax of empagliflozin | 3.00 hours | Full Range 54.6 |
| FDC Fed | Time to Maximum Measured Concentration (Tmax) | Tmax of metformin | 3.00 hours | Full Range 49.8 |