Diabetes Mellitus, Type 2
Conditions
Brief summary
Assessment of the effect of normal and impaired kidney function on the pharmacokinetics, pharmacodynamics and safety of BI 10773
Interventions
DRUGBI 10773
oral administration
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
No
Inclusion criteria
1. Male and female subjects with type 2 diabetes 2. Renally impaired male or female subjects 3. Age 18 - 75 years 4. BMI 18 - 34 kg/m2, at least 45 kg for females (Body Mass Index) 5. Signed and dated written informed consent
Exclusion criteria
1. Significant gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders as judged by the investigator. 2. Relevant gastrointestinal tract surgery 3. Diseases of the central nervous system (such as epilepsy, seizures) or psychiatric disorders or relevant neurological disorders 4. History of relevant orthostatic hypotension, fainting spells or blackouts; systolic blood pressure \< 100 or \> 160 mm Hg, diastolic blood pressure \< 60 or \> 100 mm Hg, pulse rate \< 50 or \> 100 1/min 5. Chronic or relevant acute infections 6. History of allergy/hypersensitivity (including drug allergies) that are deemed relevant to the trial as judged by the investigator 7. Use within 10 days prior to administration or during the trial of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation. Co medication known to inhibit or induce P-glycoprotein or CYP3A is not allowed. Inhibitors of P-glycoprotein or CYP3A (cytochrom P3A) are e.g. * protease inhibitors, (e.g. ritonavir, lopinavir nelfinavir) * azole antimycotics, (itraconazole, ketoconazole, miconazole) * macrolid antibiotics, (clarithromycin, erythromycin) * amiodarone, cimetidine, diltiazem, fluvoxamine, mibefradil, nefazodone, verapamil, tacrolimus, quinidine, reserpine, cyclosporine A Inducers of P-gp or CYP3A are e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, ri-fampin, St. John's wort, troglitazone. In dubious cases, a case by case decision will be made after consultation with the sponsor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Area under the concentration time curve of the analyte in plasma over the time interval from 0 to infinity. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used. |
| Cmax (Maximum Concentration of the Analyte in Plasma) | 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Maximum concentration of Empagliflozin in plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Terminal Rate Constant in Plasma | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Terminal rate constant in plasma (Lz) |
| Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Apparent clearance of the analyte in the plasma after extravascular administration |
| Apparent Volume of Distribution During the Terminal Phase Lz | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Apparent volume of distribution during the terminal phase Lz |
| AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used. |
| Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration | Amount of analyte that is eliminated in urine over the time interval 0-96 hours. |
| fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration | Fraction of analyte excreted unchanged in urine from time point 0-96 hours. |
| Time to Maximum Concentration of the Analyte in Plasma | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax) |
| %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity |
| Plasma Protein Binding | 1 h before drug administration and 1:30 and 3:00 h after drug administration | Plasma protein binding is the percent of analyte binding to the plasma protein, pre-dose plasma samples were spiked with Empa 1000 nmol/L. The standard deviation is actually the coefficient of variation. |
| Total Urinary Glucose Excretion (UGE) | 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration (Interval 24-0 h before drug administration only for baseline UGE) | Change from baseline in total urinary glucose excretion |
| Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Drug administration until end-of-study-examination, 5 days | Number of participants with clinically relevant findings in physical examination, Vital Signs, Clinically Significant Abnormalities in Electrocardiogram (ECG) and Significant Changes from Baseline Laboratory Measurements |
| Assessment of Tolerability by Investigator | Drug administration until end-of-study-examination, 5 days | Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation. |
| Renal Clearance of the Analyte in Plasma After Extravascular Administration | 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration | Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 hours. |
| Half-life and Mean Residence Time of the Analyte in Plasma | 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration | Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body |
Countries
Germany
Participant flow
Recruitment details
The trial was conducted in two trial centres as an open-label, parallel group design with one treatment period. The trial was performed in 40 male and female patients who were assigned to five treatment groups according to their creatinine clearance.
Participants by arm
| Arm | Count |
|---|---|
| Normal Renal Function Patients with type 2 diabetes and normal renal function. Normal renal function was defined as a Glomerular filtration rate of more than 90 mL/min/1.73 m².
Patients were administered once with 50 mg of Empagliflozin as a single dose by oral administration. | 8 |
| Mild Renal Impairment Patients with type 2 diabetes and mild renal impairment. Mild renal impairment was defined as a Glomerular filtration rate of 60-89 mL/min/1.73 m².
Patients were administered once with 50 mg of Empagliflozin as a single dose by oral administration. | 9 |
| Moderate Renal Impairment Patients with type 2 diabetes and moderate renal impairment. Moderate renal impairment was defined as a Glomerular filtration rate of 30-59 mL/min/1.73 m².
Patients were administered once with 50 mg of Empagliflozin as a single dose by oral administration. | 7 |
| Severe Renal Impairment Patients with severe renal impairment. Severe renal impairment was defined as a Glomerular filtration rate of less than 30 mL/min/1.73 m².
Patients were administered once with 50 mg of Empagliflozin as a single dose by oral administration. | 8 |
| Kidney Failure Patients with kidney failure, i.e. patients requiring dialysis. Patients were administered once with 50 mg of Empagliflozin as a single dose by oral administration. | 8 |
| Total | 40 |
Baseline characteristics
| Characteristic | Normal Renal Function | Mild Renal Impairment | Moderate Renal Impairment | Severe Renal Impairment | Kidney Failure | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 11.7 | 60.0 years STANDARD_DEVIATION 8.8 | 63.1 years STANDARD_DEVIATION 9.5 | 56.0 years STANDARD_DEVIATION 12.9 | 45.8 years STANDARD_DEVIATION 12 | 55.8 years STANDARD_DEVIATION 12 |
| Sex: Female, Male Female | 7 Participants | 6 Participants | 3 Participants | 1 Participants | 4 Participants | 21 Participants |
| Sex: Female, Male Male | 1 Participants | 3 Participants | 4 Participants | 7 Participants | 4 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 8 | 0 / 9 | 1 / 7 | 0 / 8 | 2 / 8 |
| serious Total, serious adverse events | 0 / 8 | 0 / 9 | 0 / 7 | 0 / 8 | 0 / 8 |
Outcome results
Primary
AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity)
Area under the concentration time curve of the analyte in plasma over the time interval from 0 to infinity. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used.
Time frame: 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: The PK analysis set (PKS) included all evaluable patients in the treated set who provided at least one observation for at least one primary (PK) endpoint without important protocol violations relevant to the evaluation of PK.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 10500 nmol*h/L | Geometric Coefficient of Variation 17.6 |
| Mild Renal Impairment | AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 12400 nmol*h/L | Geometric Coefficient of Variation 21.6 |
| Moderate Renal Impairment | AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 12600 nmol*h/L | Geometric Coefficient of Variation 27.1 |
| Severe Renal Impairment | AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 17500 nmol*h/L | Geometric Coefficient of Variation 18.9 |
| Kidney Failure | AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity) | 15600 nmol*h/L | Geometric Coefficient of Variation 38.6 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [96.17, 145.38]ANOVA
Comparison: No formal testing, investigation of relative bioavailability90% CI: [96.25, 149.47]ANOVA
Comparison: No formal testing, investigation of relative bioavailability90% CI: [134.44, 205.68]ANOVA
Comparison: No formal testing, investigation of relative bioavailability90% CI: [119.89, 183.42]ANOVA
Primary
Cmax (Maximum Concentration of the Analyte in Plasma)
Maximum concentration of Empagliflozin in plasma
Time frame: 1 hour (h) before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Cmax (Maximum Concentration of the Analyte in Plasma) | 1210 nmol/L | Geometric Coefficient of Variation 24.1 |
| Mild Renal Impairment | Cmax (Maximum Concentration of the Analyte in Plasma) | 1430 nmol/L | Geometric Coefficient of Variation 33.1 |
| Moderate Renal Impairment | Cmax (Maximum Concentration of the Analyte in Plasma) | 1230 nmol/L | Geometric Coefficient of Variation 30.9 |
| Severe Renal Impairment | Cmax (Maximum Concentration of the Analyte in Plasma) | 1450 nmol/L | Geometric Coefficient of Variation 33 |
| Kidney Failure | Cmax (Maximum Concentration of the Analyte in Plasma) | 1250 nmol/L | Geometric Coefficient of Variation 25.9 |
Comparison: No formal testing, investigation of relative bioavailability90% CI: [93.62, 150.84]ANOVA
Comparison: No formal testing, investigation of relative bioavailability90% CI: [79.33, 131.85]ANOVA
Comparison: No formal testing, investigation of relative bioavailability90% CI: [94.42, 154.25]ANOVA
Comparison: No formal testing, investigation of relative bioavailability95% CI: [81.18, 132.61]ANOVA
Secondary
Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h)
Amount of analyte that is eliminated in urine over the time interval 0-96 hours.
Time frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 17300 nmol | Geometric Coefficient of Variation 26.1 |
| Mild Renal Impairment | Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 12100 nmol | Geometric Coefficient of Variation 43.8 |
| Moderate Renal Impairment | Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 6840 nmol | Geometric Coefficient of Variation 85.5 |
| Severe Renal Impairment | Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 3730 nmol | Geometric Coefficient of Variation 49.3 |
| Kidney Failure | Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h) | 300 nmol | Geometric Coefficient of Variation 117 |
Secondary
Apparent Clearance of the Analyte in the Plasma After Extravascular Administration
Apparent clearance of the analyte in the plasma after extravascular administration
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 176 mL/min | Geometric Coefficient of Variation 17.6 |
| Mild Renal Impairment | Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 149 mL/min | Geometric Coefficient of Variation 21.6 |
| Moderate Renal Impairment | Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 147 mL/min | Geometric Coefficient of Variation 27.1 |
| Severe Renal Impairment | Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 106 mL/min | Geometric Coefficient of Variation 18.9 |
| Kidney Failure | Apparent Clearance of the Analyte in the Plasma After Extravascular Administration | 119 mL/min | Geometric Coefficient of Variation 38.6 |
Secondary
Apparent Volume of Distribution During the Terminal Phase Lz
Apparent volume of distribution during the terminal phase Lz
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Apparent Volume of Distribution During the Terminal Phase Lz | 266 L | Geometric Coefficient of Variation 55.1 |
| Mild Renal Impairment | Apparent Volume of Distribution During the Terminal Phase Lz | 248 L | Geometric Coefficient of Variation 76.3 |
| Moderate Renal Impairment | Apparent Volume of Distribution During the Terminal Phase Lz | 248 L | Geometric Coefficient of Variation 55.5 |
| Severe Renal Impairment | Apparent Volume of Distribution During the Terminal Phase Lz | 206 L | Geometric Coefficient of Variation 78 |
| Kidney Failure | Apparent Volume of Distribution During the Terminal Phase Lz | 190 L | Geometric Coefficient of Variation 45.1 |
Secondary
Assessment of Tolerability by Investigator
Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation.
Time frame: Drug administration until end-of-study-examination, 5 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Renal Function | Assessment of Tolerability by Investigator | Bad | 0 participants |
| Normal Renal Function | Assessment of Tolerability by Investigator | Good | 8 participants |
| Normal Renal Function | Assessment of Tolerability by Investigator | Not assessable | 0 participants |
| Normal Renal Function | Assessment of Tolerability by Investigator | Satisfactory | 0 participants |
| Normal Renal Function | Assessment of Tolerability by Investigator | Not satisfactory | 0 participants |
| Mild Renal Impairment | Assessment of Tolerability by Investigator | Bad | 0 participants |
| Mild Renal Impairment | Assessment of Tolerability by Investigator | Not satisfactory | 0 participants |
| Mild Renal Impairment | Assessment of Tolerability by Investigator | Satisfactory | 0 participants |
| Mild Renal Impairment | Assessment of Tolerability by Investigator | Not assessable | 0 participants |
| Mild Renal Impairment | Assessment of Tolerability by Investigator | Good | 9 participants |
| Moderate Renal Impairment | Assessment of Tolerability by Investigator | Not satisfactory | 0 participants |
| Moderate Renal Impairment | Assessment of Tolerability by Investigator | Good | 7 participants |
| Moderate Renal Impairment | Assessment of Tolerability by Investigator | Satisfactory | 0 participants |
| Moderate Renal Impairment | Assessment of Tolerability by Investigator | Bad | 0 participants |
| Moderate Renal Impairment | Assessment of Tolerability by Investigator | Not assessable | 0 participants |
| Severe Renal Impairment | Assessment of Tolerability by Investigator | Not assessable | 0 participants |
| Severe Renal Impairment | Assessment of Tolerability by Investigator | Good | 8 participants |
| Severe Renal Impairment | Assessment of Tolerability by Investigator | Bad | 0 participants |
| Severe Renal Impairment | Assessment of Tolerability by Investigator | Not satisfactory | 0 participants |
| Severe Renal Impairment | Assessment of Tolerability by Investigator | Satisfactory | 0 participants |
| Kidney Failure | Assessment of Tolerability by Investigator | Not satisfactory | 0 participants |
| Kidney Failure | Assessment of Tolerability by Investigator | Bad | 0 participants |
| Kidney Failure | Assessment of Tolerability by Investigator | Good | 8 participants |
| Kidney Failure | Assessment of Tolerability by Investigator | Not assessable | 0 participants |
| Kidney Failure | Assessment of Tolerability by Investigator | Satisfactory | 0 participants |
Secondary
AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point)
Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point. The areas under the curve were calculated using the linear up/log down algorithm. If a drug concentration was equal to or higher than the preceding concentration, the linear trapezoidal method was used. If the drug concentration was smaller than the preceding concentration, the logarithmic method was used.
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 10300 nmol*h/L | Geometric Coefficient of Variation 17.5 |
| Mild Renal Impairment | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 12100 nmol*h/L | Geometric Coefficient of Variation 20.9 |
| Moderate Renal Impairment | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 12100 nmol*h/L | Geometric Coefficient of Variation 24.4 |
| Severe Renal Impairment | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 16500 nmol*h/L | Geometric Coefficient of Variation 19.9 |
| Kidney Failure | AUC0-tz (Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From 0 to the Time of the Last Quantifiable Data Point) | 14900 nmol*h/L | Geometric Coefficient of Variation 34.4 |
Secondary
%AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity)
Percentage of area under the concentration-time curve of the analyte in plasma over the time interval from the time of the last quantifiable data point extrapolated to infinity
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 0.869 percent | Geometric Coefficient of Variation 225 |
| Mild Renal Impairment | %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 1.07 percent | Geometric Coefficient of Variation 243 |
| Moderate Renal Impairment | %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 1.21 percent | Geometric Coefficient of Variation 223 |
| Severe Renal Impairment | %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 1.78 percent | Geometric Coefficient of Variation 334 |
| Kidney Failure | %AUCtz-∞ (Percentage of Area Under the Concentration-time Curve of the Analyte in Plasma Over the Time Interval From the Time of the Last Quantifiable Data Point Extrapolated to Infinity) | 1.14 percent | Geometric Coefficient of Variation 330 |
Secondary
fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours)
Fraction of analyte excreted unchanged in urine from time point 0-96 hours.
Time frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 15.6 percentage of analyte | Geometric Coefficient of Variation 26.1 |
| Mild Renal Impairment | fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 10.9 percentage of analyte | Geometric Coefficient of Variation 43.8 |
| Moderate Renal Impairment | fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 6.16 percentage of analyte | Geometric Coefficient of Variation 85.5 |
| Severe Renal Impairment | fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 3.36 percentage of analyte | Geometric Coefficient of Variation 49.3 |
| Kidney Failure | fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours) | 0.271 percentage of analyte | Geometric Coefficient of Variation 117 |
Secondary
Half-life and Mean Residence Time of the Analyte in Plasma
Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Half-life and Mean Residence Time of the Analyte in Plasma | Terminal half-life | 17.4 h | Geometric Coefficient of Variation 57.4 |
| Normal Renal Function | Half-life and Mean Residence Time of the Analyte in Plasma | Mean residence time | 13.1 h | Geometric Coefficient of Variation 37.4 |
| Mild Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Terminal half-life | 19.3 h | Geometric Coefficient of Variation 81.6 |
| Mild Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Mean residence time | 15.7 h | Geometric Coefficient of Variation 44.6 |
| Moderate Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Terminal half-life | 19.5 h | Geometric Coefficient of Variation 63.9 |
| Moderate Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Mean residence time | 18.4 h | Geometric Coefficient of Variation 52.7 |
| Severe Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Mean residence time | 22.2 h | Geometric Coefficient of Variation 57.6 |
| Severe Renal Impairment | Half-life and Mean Residence Time of the Analyte in Plasma | Terminal half-life | 22.5 h | Geometric Coefficient of Variation 74.3 |
| Kidney Failure | Half-life and Mean Residence Time of the Analyte in Plasma | Terminal half-life | 18.5 h | Geometric Coefficient of Variation 62.6 |
| Kidney Failure | Half-life and Mean Residence Time of the Analyte in Plasma | Mean residence time | 19.8 h | Geometric Coefficient of Variation 51.2 |
Secondary
Plasma Protein Binding
Plasma protein binding is the percent of analyte binding to the plasma protein, pre-dose plasma samples were spiked with Empa 1000 nmol/L. The standard deviation is actually the coefficient of variation.
Time frame: 1 h before drug administration and 1:30 and 3:00 h after drug administration
Population: PKS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Normal Renal Function | Plasma Protein Binding | Pre-dose | 83.61 percentage of plasma protein binding | Standard Deviation 1.1 |
| Normal Renal Function | Plasma Protein Binding | 3:00 h after dosing | 83.94 percentage of plasma protein binding | Standard Deviation 1.88 |
| Normal Renal Function | Plasma Protein Binding | 1:30 h after dosing | 85.18 percentage of plasma protein binding | Standard Deviation 1.91 |
| Mild Renal Impairment | Plasma Protein Binding | 1:30 h after dosing | 83.70 percentage of plasma protein binding | Standard Deviation 2.49 |
| Mild Renal Impairment | Plasma Protein Binding | Pre-dose | 82.72 percentage of plasma protein binding | Standard Deviation 3.36 |
| Mild Renal Impairment | Plasma Protein Binding | 3:00 h after dosing | 83.18 percentage of plasma protein binding | Standard Deviation 2.58 |
| Moderate Renal Impairment | Plasma Protein Binding | 1:30 h after dosing | 82.68 percentage of plasma protein binding | Standard Deviation 2.76 |
| Moderate Renal Impairment | Plasma Protein Binding | Pre-dose | 81.29 percentage of plasma protein binding | Standard Deviation 2.48 |
| Moderate Renal Impairment | Plasma Protein Binding | 3:00 h after dosing | 81.90 percentage of plasma protein binding | Standard Deviation 1.69 |
| Severe Renal Impairment | Plasma Protein Binding | Pre-dose | 79.98 percentage of plasma protein binding | Standard Deviation 2.42 |
| Severe Renal Impairment | Plasma Protein Binding | 3:00 h after dosing | 80.38 percentage of plasma protein binding | Standard Deviation 1.61 |
| Severe Renal Impairment | Plasma Protein Binding | 1:30 h after dosing | 81.02 percentage of plasma protein binding | Standard Deviation 1.73 |
| Kidney Failure | Plasma Protein Binding | 1:30 h after dosing | 81.09 percentage of plasma protein binding | Standard Deviation 1.94 |
| Kidney Failure | Plasma Protein Binding | Pre-dose | 81.08 percentage of plasma protein binding | Standard Deviation 1.54 |
| Kidney Failure | Plasma Protein Binding | 3:00 h after dosing | 80.32 percentage of plasma protein binding | Standard Deviation 2 |
Secondary
Renal Clearance of the Analyte in Plasma After Extravascular Administration
Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 hours.
Time frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Renal Clearance of the Analyte in Plasma After Extravascular Administration | 28.0 mL/min | Geometric Coefficient of Variation 19.5 |
| Mild Renal Impairment | Renal Clearance of the Analyte in Plasma After Extravascular Administration | 16.7 mL/min | Geometric Coefficient of Variation 53.7 |
| Moderate Renal Impairment | Renal Clearance of the Analyte in Plasma After Extravascular Administration | 9.39 mL/min | Geometric Coefficient of Variation 87.9 |
| Severe Renal Impairment | Renal Clearance of the Analyte in Plasma After Extravascular Administration | 3.70 mL/min | Geometric Coefficient of Variation 38.5 |
| Kidney Failure | Renal Clearance of the Analyte in Plasma After Extravascular Administration | 0.349 mL/min | Geometric Coefficient of Variation 188 |
Secondary
Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
Number of participants with clinically relevant findings in physical examination, Vital Signs, Clinically Significant Abnormalities in Electrocardiogram (ECG) and Significant Changes from Baseline Laboratory Measurements
Time frame: Drug administration until end-of-study-examination, 5 days
Population: Treated set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Normal Renal Function | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | ECG | 0 participants |
| Normal Renal Function | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Physical examination | 0 participants |
| Normal Renal Function | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Laboratory Measurements | 0 participants |
| Normal Renal Function | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Vital signs | 0 participants |
| Mild Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Physical examination | 0 participants |
| Mild Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Laboratory Measurements | 0 participants |
| Mild Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Vital signs | 0 participants |
| Mild Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | ECG | 0 participants |
| Moderate Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Vital signs | 0 participants |
| Moderate Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Laboratory Measurements | 0 participants |
| Moderate Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Physical examination | 0 participants |
| Moderate Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | ECG | 0 participants |
| Severe Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Vital signs | 0 participants |
| Severe Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Physical examination | 0 participants |
| Severe Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | ECG | 0 participants |
| Severe Renal Impairment | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Laboratory Measurements | 0 participants |
| Kidney Failure | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | ECG | 0 participants |
| Kidney Failure | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Physical examination | 0 participants |
| Kidney Failure | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Vital signs | 0 participants |
| Kidney Failure | Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements | Laboratory Measurements | 0 participants |
Secondary
Terminal Rate Constant in Plasma
Terminal rate constant in plasma (Lz)
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Terminal Rate Constant in Plasma | 0.0398 1/h | Geometric Coefficient of Variation 57.4 |
| Mild Renal Impairment | Terminal Rate Constant in Plasma | 0.0360 1/h | Geometric Coefficient of Variation 81.6 |
| Moderate Renal Impairment | Terminal Rate Constant in Plasma | 0.0355 1/h | Geometric Coefficient of Variation 63.9 |
| Severe Renal Impairment | Terminal Rate Constant in Plasma | 0.0308 1/h | Geometric Coefficient of Variation 74.3 |
| Kidney Failure | Terminal Rate Constant in Plasma | 0.0375 1/h | Geometric Coefficient of Variation 62.6 |
Secondary
Time to Maximum Concentration of the Analyte in Plasma
Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax)
Time frame: 1 h before drug administration and 0:20, 0:40, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 14:00, 24:00, 36:00. 48:00, 72:00, 96:00 h after drug administration
Population: PKS
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Normal Renal Function | Time to Maximum Concentration of the Analyte in Plasma | 1.00 h |
| Mild Renal Impairment | Time to Maximum Concentration of the Analyte in Plasma | 2.50 h |
| Moderate Renal Impairment | Time to Maximum Concentration of the Analyte in Plasma | 2.00 h |
| Severe Renal Impairment | Time to Maximum Concentration of the Analyte in Plasma | 2.00 h |
| Kidney Failure | Time to Maximum Concentration of the Analyte in Plasma | 2.50 h |
Secondary
Total Urinary Glucose Excretion (UGE)
Change from baseline in total urinary glucose excretion
Time frame: 24-0 h before drug administration and 0-4, 4-8, 8-12, 12-24, 24-36, 36-48, 48-72, 72-96 hours after drug administration (Interval 24-0 h before drug administration only for baseline UGE)
Population: The UGE analysis set included all patients in the treated set who provided the baseline value from 0 to 24 hours before drug administration and the value for urinary glucose excretion from 0 to 24 hours after drug administration without important protocol violations relevant to the evaluation of Pharmacodynamics.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Renal Function | Total Urinary Glucose Excretion (UGE) | 97643 mg | Standard Error 7204 |
| Mild Renal Impairment | Total Urinary Glucose Excretion (UGE) | 61590 mg | Standard Error 6892 |
| Moderate Renal Impairment | Total Urinary Glucose Excretion (UGE) | 55674 mg | Standard Error 16891 |
| Severe Renal Impairment | Total Urinary Glucose Excretion (UGE) | 18251 mg | Standard Error 3925 |
| Kidney Failure | Total Urinary Glucose Excretion (UGE) | 779 mg | Standard Error 904 |