Healthy, Hepatic Insufficiency
Conditions
Brief summary
The main objective of this study is to assess the effect of mild, moderate and severe hepatic impairment on the pharmacokinetics, safety and tolerability of BI 10773 following oral administration of BI 10773 as a single dose.
Interventions
DRUGBI 10773
2 tablets BI 10773 25 mg single dose
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy males and females. Hepatically impaired male and female subjects. Age: 18 - 75 years, BMI: 18-34 kg/m2 Creatinine clearance \>80 mL/min (except for patients with severe hepatic impairment, see
Exclusion criteria
. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve 0 to Infinity (AUC0-∞) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
| Maximum Measured Concentration (Cmax) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Maximum measured concentration of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Rate Constant (λz) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Terminal rate constant in plasma. The standard deviation is actually the coefficient of variation. |
| Terminal Half-Life (t1/2) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Terminal half-life of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation. |
| Mean Residence Time (MRTpo) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Mean residence time of empagliflozin (empa) in the body. The standard deviation is actually the coefficient of variation. |
| Apparent Clearance After Extravascular Administration (CL/F) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Apparent clearance of empagliflozin (empa) in the plasma after extravascular administration. The standard deviation is actually the coefficient of variation. |
| Apparent Volume of Distribution During the Terminal Phase (Vz/F) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Apparent volume of distribution during the terminal phase (λz). The standard deviation is actually the coefficient of variation. |
| Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h 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. The standard deviation is actually the coefficient of variation. |
| Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) | Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration | Fraction of empagliflozin (empa) excreted unchanged in urine from time points 0 to 96 hours. The standard deviation is actually the coefficient of variation. |
| Renal Clearance After Extravascular Administration (CL R) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration | Renal clearance of empagliflozin (empa) in plasma after extravascular administration. The standard deviation is actually the coefficient of variation. |
| Urinary Glucose Excretion (UGE) | Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration | Urinary glucose excretion, this endpoint was measured using Ae0-96. The standard deviation is actually the coefficient of variation. |
| Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days | Clinically relevant abnormalities for physical examination, vital signs, ECG, clinical laboratory tests and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AE). |
| Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) | Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration | Amount of empagliflozin (empa) that is eliminated in urine over the time interval 0 to 96 hours. The standard deviation is actually the coefficient of variation. |
| Time From Dosing to Maximum Concentration (Tmax) | Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration. | Time from dosing to maximum concentration of empagliflozin (empa) in plasma. |
Countries
Romania
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight. | 12 |
| Mild Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A. | 8 |
| Moderate Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B. | 8 |
| Severe Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C. | 8 |
| Total | 36 |
Baseline characteristics
| Characteristic | Healthy | Mild | Moderate | Severe | Total |
|---|---|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 9.2 | 57.0 years STANDARD_DEVIATION 6.9 | 51.0 years STANDARD_DEVIATION 8.5 | 53.9 years STANDARD_DEVIATION 9.6 | 53.9 years STANDARD_DEVIATION 8.6 |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 3 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 5 Participants | 4 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 12 | 0 / 8 | 3 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 12 | 0 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
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. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Area Under the Curve 0 to Infinity (AUC0-∞) | 10800 nmol*h/L | Standard Deviation 22.6 |
| Mild | Area Under the Curve 0 to Infinity (AUC0-∞) | 13800 nmol*h/L | Standard Deviation 38.6 |
| Moderate | Area Under the Curve 0 to Infinity (AUC0-∞) | 16100 nmol*h/L | Standard Deviation 26.2 |
| Severe | Area Under the Curve 0 to Infinity (AUC0-∞) | 19000 nmol*h/L | Standard Deviation 27.1 |
Comparison: Ratio calculated as mild divided by healthy90% CI: [98.89, 153.36]ANOVA
Comparison: Ratio calculated as moderate divided by healthy90% CI: [118.02, 183.02]ANOVA
Comparison: Ratio calculated as severe divided by healthy90% CI: [140.29, 217.55]ANOVA
Primary
Maximum Measured Concentration (Cmax)
Maximum measured concentration of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Maximum Measured Concentration (Cmax) | 1370 nmol/L | Standard Deviation 33.9 |
| Mild | Maximum Measured Concentration (Cmax) | 1430 nmol/L | Standard Deviation 36.8 |
| Moderate | Maximum Measured Concentration (Cmax) | 1660 nmol/L | Standard Deviation 26.4 |
| Severe | Maximum Measured Concentration (Cmax) | 1970 nmol/L | Standard Deviation 22.1 |
Comparison: Ratio calculated as mild divided by healthy90% CI: [82.29, 130.95]ANOVA
Comparison: Ratio calculated as moderate divided by healthy90% CI: [97.74, 155.55]ANOVA
Comparison: Ratio calculated as severe divided by healthy90% CI: [117.65, 187.23]ANOVA
Secondary
Amount of Empagliflozin That is Eliminated in Urine (Ae0-96)
Amount of empagliflozin (empa) that is eliminated in urine over the time interval 0 to 96 hours. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) | 18400 nmol | Standard Deviation 26.5 |
| Mild | Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) | 16900 nmol | Standard Deviation 20.6 |
| Moderate | Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) | 18500 nmol | Standard Deviation 35 |
| Severe | Amount of Empagliflozin That is Eliminated in Urine (Ae0-96) | 22500 nmol | Standard Deviation 23.5 |
Secondary
Apparent Clearance After Extravascular Administration (CL/F)
Apparent clearance of empagliflozin (empa) in the plasma after extravascular administration. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Apparent Clearance After Extravascular Administration (CL/F) | 179 mL/min | Standard Deviation 23.9 |
| Mild | Apparent Clearance After Extravascular Administration (CL/F) | 150 mL/min | Standard Deviation 34.4 |
| Moderate | Apparent Clearance After Extravascular Administration (CL/F) | 124 mL/min | Standard Deviation 30.7 |
| Severe | Apparent Clearance After Extravascular Administration (CL/F) | 103 mL/min | Standard Deviation 23 |
Secondary
Apparent Volume of Distribution During the Terminal Phase (Vz/F)
Apparent volume of distribution during the terminal phase (λz). The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 298 L | Standard Deviation 39.5 |
| Mild | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 237 L | Standard Deviation 45.5 |
| Moderate | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 173 L | Standard Deviation 35 |
| Severe | Apparent Volume of Distribution During the Terminal Phase (Vz/F) | 144 L | Standard Deviation 46.7 |
Secondary
Area Under the Curve 0 to Time of 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. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration.
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 10700 nmol*h/L | Standard Deviation 22.6 |
| Mild | Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 13700 nmol*h/L | Standard Deviation 38.4 |
| Moderate | Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 15800 nmol*h/L | Standard Deviation 25.7 |
| Severe | Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz) | 18600 nmol*h/L | Standard Deviation 23.9 |
Secondary
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator
Clinically relevant abnormalities for physical examination, vital signs, ECG, clinical laboratory tests and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AE).
Time frame: Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Population: Treated Set (TS) included all subjects who had been dispensed study medication and were documented to have taken the investigational treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Healthy | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Electrocardiogram abnormal | 2 participants |
| Healthy | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Nitrite urine present | 0 participants |
| Mild | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Nitrite urine present | 0 participants |
| Mild | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Electrocardiogram abnormal | 0 participants |
| Moderate | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Electrocardiogram abnormal | 0 participants |
| Moderate | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Nitrite urine present | 0 participants |
| Severe | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Electrocardiogram abnormal | 0 participants |
| Severe | Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator | Investigations: Nitrite urine present | 1 participants |
Secondary
Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96))
Fraction of empagliflozin (empa) excreted unchanged in urine from time points 0 to 96 hours. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) | 16.6 percentage of empagliflozin | Standard Deviation 26.5 |
| Mild | Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) | 15.2 percentage of empagliflozin | Standard Deviation 20.6 |
| Moderate | Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) | 16.7 percentage of empagliflozin | Standard Deviation 35 |
| Severe | Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96)) | 20.3 percentage of empagliflozin | Standard Deviation 23.5 |
Secondary
Mean Residence Time (MRTpo)
Mean residence time of empagliflozin (empa) in the body. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Mean Residence Time (MRTpo) | 13.2 h | Standard Deviation 31.3 |
| Mild | Mean Residence Time (MRTpo) | 14.4 h | Standard Deviation 22.9 |
| Moderate | Mean Residence Time (MRTpo) | 15.5 h | Standard Deviation 37.2 |
| Severe | Mean Residence Time (MRTpo) | 15.7 h | Standard Deviation 43 |
Secondary
Renal Clearance After Extravascular Administration (CL R)
Renal clearance of empagliflozin (empa) in plasma after extravascular administration. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Renal Clearance After Extravascular Administration (CL R) | 28.7 mL/min | Standard Deviation 30.3 |
| Mild | Renal Clearance After Extravascular Administration (CL R) | 23.7 mL/min | Standard Deviation 48 |
| Moderate | Renal Clearance After Extravascular Administration (CL R) | 19.9 mL/min | Standard Deviation 36.8 |
| Severe | Renal Clearance After Extravascular Administration (CL R) | 21.3 mL/min | Standard Deviation 37.1 |
Secondary
Terminal Half-Life (t1/2)
Terminal half-life of empagliflozin (empa) in plasma. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Terminal Half-Life (t1/2) | 19.9 h | Standard Deviation 43.1 |
| Mild | Terminal Half-Life (t1/2) | 18.1 h | Standard Deviation 25.9 |
| Moderate | Terminal Half-Life (t1/2) | 17.1 h | Standard Deviation 45.9 |
| Severe | Terminal Half-Life (t1/2) | 17.7 h | Standard Deviation 67.4 |
Secondary
Terminal Rate Constant (λz)
Terminal rate constant in plasma. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Terminal Rate Constant (λz) | 0.0414 1/h | Standard Deviation 41.6 |
| Mild | Terminal Rate Constant (λz) | 0.0404 1/h | Standard Deviation 23.5 |
| Moderate | Terminal Rate Constant (λz) | 0.0454 1/h | Standard Deviation 28.9 |
| Severe | Terminal Rate Constant (λz) | 0.0506 1/h | Standard Deviation 41.1 |
Secondary
Time From Dosing to Maximum Concentration (Tmax)
Time from dosing to maximum concentration of empagliflozin (empa) in plasma.
Time frame: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration.
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Healthy | Time From Dosing to Maximum Concentration (Tmax) | 2.00 h | Full Range 50.1 |
| Mild | Time From Dosing to Maximum Concentration (Tmax) | 1.50 h | Full Range 73.2 |
| Moderate | Time From Dosing to Maximum Concentration (Tmax) | 2.00 h | Full Range 64.4 |
| Severe | Time From Dosing to Maximum Concentration (Tmax) | 1.50 h | Full Range 48.2 |
Secondary
Urinary Glucose Excretion (UGE)
Urinary glucose excretion, this endpoint was measured using Ae0-96. The standard deviation is actually the coefficient of variation.
Time frame: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration
Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy | Urinary Glucose Excretion (UGE) | 86600 mg | Standard Deviation 34.8 |
| Mild | Urinary Glucose Excretion (UGE) | 81000 mg | Standard Deviation 26.7 |
| Moderate | Urinary Glucose Excretion (UGE) | 79700 mg | Standard Deviation 67.9 |
| Severe | Urinary Glucose Excretion (UGE) | 79800 mg | Standard Deviation 45.6 |