Trial Outcomes & Findings for Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BI 10773 in Type II Diabetes Patients With Different Degrees of Renal Impairment (NCT NCT01907113)
NCT ID: NCT01907113
Last Updated: 2014-07-14
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
40 participants
Primary outcome timeframe
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
Results posted on
2014-07-14
Participant Flow
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.
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
8
|
9
|
7
|
8
|
8
|
|
Overall Study
COMPLETED
|
8
|
9
|
7
|
8
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BI 10773 in Type II Diabetes Patients With Different Degrees of Renal Impairment
Baseline characteristics by cohort
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
54.5 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
60.0 years
STANDARD_DEVIATION 8.8 • n=7 Participants
|
63.1 years
STANDARD_DEVIATION 9.5 • n=5 Participants
|
56.0 years
STANDARD_DEVIATION 12.9 • n=4 Participants
|
45.8 years
STANDARD_DEVIATION 12.0 • n=21 Participants
|
55.8 years
STANDARD_DEVIATION 12.0 • n=8 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
21 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
19 Participants
n=8 Participants
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: 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.
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.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
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
|
12400 nmol*h/L
Geometric Coefficient of Variation 21.6
|
12600 nmol*h/L
Geometric Coefficient of Variation 27.1
|
17500 nmol*h/L
Geometric Coefficient of Variation 18.9
|
15600 nmol*h/L
Geometric Coefficient of Variation 38.6
|
PRIMARY outcome
Timeframe: 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 administrationPopulation: PKS
Maximum concentration of Empagliflozin in plasma
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Cmax (Maximum Concentration of the Analyte in Plasma)
|
1210 nmol/L
Geometric Coefficient of Variation 24.1
|
1430 nmol/L
Geometric Coefficient of Variation 33.1
|
1230 nmol/L
Geometric Coefficient of Variation 30.9
|
1450 nmol/L
Geometric Coefficient of Variation 33.0
|
1250 nmol/L
Geometric Coefficient of Variation 25.9
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Time from last dosing to maximum concentration of Empagliflozin in plasma (tmax)
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Time to Maximum Concentration of the Analyte in Plasma
|
1.00 h
Interval 1.0 to 3.0
|
2.50 h
Interval 2.0 to 4.0
|
2.00 h
Interval 1.5 to 3.0
|
2.00 h
Interval 0.67 to 4.0
|
2.50 h
Interval 1.5 to 3.0
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Terminal half-life of Empagliflozin (t1/2) and Mean residence time of Empagliflozin in the body
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Half-life and Mean Residence Time of the Analyte in Plasma
Terminal half-life
|
17.4 h
Geometric Coefficient of Variation 57.4
|
19.3 h
Geometric Coefficient of Variation 81.6
|
19.5 h
Geometric Coefficient of Variation 63.9
|
22.5 h
Geometric Coefficient of Variation 74.3
|
18.5 h
Geometric Coefficient of Variation 62.6
|
|
Half-life and Mean Residence Time of the Analyte in Plasma
Mean residence time
|
13.1 h
Geometric Coefficient of Variation 37.4
|
15.7 h
Geometric Coefficient of Variation 44.6
|
18.4 h
Geometric Coefficient of Variation 52.7
|
22.2 h
Geometric Coefficient of Variation 57.6
|
19.8 h
Geometric Coefficient of Variation 51.2
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Terminal rate constant in plasma (Lz)
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Terminal Rate Constant in Plasma
|
0.0398 1/h
Geometric Coefficient of Variation 57.4
|
0.0360 1/h
Geometric Coefficient of Variation 81.6
|
0.0355 1/h
Geometric Coefficient of Variation 63.9
|
0.0308 1/h
Geometric Coefficient of Variation 74.3
|
0.0375 1/h
Geometric Coefficient of Variation 62.6
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Apparent clearance of the analyte in the plasma after extravascular administration
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Apparent Clearance of the Analyte in the Plasma After Extravascular Administration
|
176 mL/min
Geometric Coefficient of Variation 17.6
|
149 mL/min
Geometric Coefficient of Variation 21.6
|
147 mL/min
Geometric Coefficient of Variation 27.1
|
106 mL/min
Geometric Coefficient of Variation 18.9
|
119 mL/min
Geometric Coefficient of Variation 38.6
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Apparent volume of distribution during the terminal phase Lz
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase Lz
|
266 L
Geometric Coefficient of Variation 55.1
|
248 L
Geometric Coefficient of Variation 76.3
|
248 L
Geometric Coefficient of Variation 55.5
|
206 L
Geometric Coefficient of Variation 78.0
|
190 L
Geometric Coefficient of Variation 45.1
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
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.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
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
|
12100 nmol*h/L
Geometric Coefficient of Variation 20.9
|
12100 nmol*h/L
Geometric Coefficient of Variation 24.4
|
16500 nmol*h/L
Geometric Coefficient of Variation 19.9
|
14900 nmol*h/L
Geometric Coefficient of Variation 34.4
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Amount of analyte that is eliminated in urine over the time interval 0-96 hours.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
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
|
12100 nmol
Geometric Coefficient of Variation 43.8
|
6840 nmol
Geometric Coefficient of Variation 85.5
|
3730 nmol
Geometric Coefficient of Variation 49.3
|
300 nmol
Geometric Coefficient of Variation 117
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Fraction of analyte excreted unchanged in urine from time point 0-96 hours.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
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
|
10.9 percentage of analyte
Geometric Coefficient of Variation 43.8
|
6.16 percentage of analyte
Geometric Coefficient of Variation 85.5
|
3.36 percentage of analyte
Geometric Coefficient of Variation 49.3
|
0.271 percentage of analyte
Geometric Coefficient of Variation 117
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
Renal Clearance of the Analyte in Plasma After Extravascular Administration for time interval 0-96 hours.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Renal Clearance of the Analyte in Plasma After Extravascular Administration
|
28.0 mL/min
Geometric Coefficient of Variation 19.5
|
16.7 mL/min
Geometric Coefficient of Variation 53.7
|
9.39 mL/min
Geometric Coefficient of Variation 87.9
|
3.70 mL/min
Geometric Coefficient of Variation 38.5
|
0.349 mL/min
Geometric Coefficient of Variation 188
|
SECONDARY outcome
Timeframe: 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 administrationPopulation: PKS
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
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
%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
|
1.07 percent
Geometric Coefficient of Variation 243
|
1.21 percent
Geometric Coefficient of Variation 223
|
1.78 percent
Geometric Coefficient of Variation 334
|
1.14 percent
Geometric Coefficient of Variation 330
|
SECONDARY outcome
Timeframe: 1 h before drug administration and 1:30 and 3:00 h after drug administrationPopulation: PKS
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.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=8 Participants
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.
|
Moderate Renal Impairment
n=8 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Plasma Protein Binding
Pre-dose
|
83.61 percentage of plasma protein binding
Standard Deviation 1.10
|
82.72 percentage of plasma protein binding
Standard Deviation 3.36
|
81.29 percentage of plasma protein binding
Standard Deviation 2.48
|
79.98 percentage of plasma protein binding
Standard Deviation 2.42
|
81.08 percentage of plasma protein binding
Standard Deviation 1.54
|
|
Plasma Protein Binding
1:30 h after dosing
|
85.18 percentage of plasma protein binding
Standard Deviation 1.91
|
83.70 percentage of plasma protein binding
Standard Deviation 2.49
|
82.68 percentage of plasma protein binding
Standard Deviation 2.76
|
81.02 percentage of plasma protein binding
Standard Deviation 1.73
|
81.09 percentage of plasma protein binding
Standard Deviation 1.94
|
|
Plasma Protein Binding
3:00 h after dosing
|
83.94 percentage of plasma protein binding
Standard Deviation 1.88
|
83.18 percentage of plasma protein binding
Standard Deviation 2.58
|
81.90 percentage of plasma protein binding
Standard Deviation 1.69
|
80.38 percentage of plasma protein binding
Standard Deviation 1.61
|
80.32 percentage of plasma protein binding
Standard Deviation 2.00
|
SECONDARY outcome
Timeframe: 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.
Change from baseline in total urinary glucose excretion
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=7 Participants
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.
|
Moderate Renal Impairment
n=5 Participants
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.
|
Severe Renal Impairment
n=6 Participants
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.
|
Kidney Failure
n=5 Participants
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.
|
|---|---|---|---|---|---|
|
Total Urinary Glucose Excretion (UGE)
|
97643 mg
Standard Error 7204
|
61590 mg
Standard Error 6892
|
55674 mg
Standard Error 16891
|
18251 mg
Standard Error 3925
|
779 mg
Standard Error 904
|
SECONDARY outcome
Timeframe: Drug administration until end-of-study-examination, 5 daysPopulation: Treated set
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
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
Physical examination
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
Vital signs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
ECG
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
Laboratory Measurements
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Drug administration until end-of-study-examination, 5 daysPopulation: Treated set
Tolerability was assessed by the investigator based on adverse events and the laboratory evaluation.
Outcome measures
| Measure |
Normal Renal Function
n=8 Participants
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.
|
Mild Renal Impairment
n=9 Participants
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.
|
Moderate Renal Impairment
n=7 Participants
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.
|
Severe Renal Impairment
n=8 Participants
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.
|
Kidney Failure
n=8 Participants
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.
|
|---|---|---|---|---|---|
|
Assessment of Tolerability by Investigator
Not assessable
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Assessment of Tolerability by Investigator
Good
|
8 participants
|
9 participants
|
7 participants
|
8 participants
|
8 participants
|
|
Assessment of Tolerability by Investigator
Satisfactory
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Assessment of Tolerability by Investigator
Not satisfactory
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Assessment of Tolerability by Investigator
Bad
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
Adverse Events
Normal Renal Function
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Mild Renal Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Moderate Renal Impairment
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Severe Renal Impairment
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Kidney Failure
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Normal Renal Function
n=8 participants at risk
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.
|
Mild Renal Impairment
n=9 participants at risk
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.
|
Moderate Renal Impairment
n=7 participants at risk
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.
|
Severe Renal Impairment
n=8 participants at risk
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.
|
Kidney Failure
n=8 participants at risk
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.
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/9 • From drug administration until end of trial examination, 5 days
|
0.00%
0/7 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
12.5%
1/8 • From drug administration until end of trial examination, 5 days
|
|
Gastrointestinal disorders
Nausea
|
12.5%
1/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/9 • From drug administration until end of trial examination, 5 days
|
0.00%
0/7 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
|
Nervous system disorders
Headache
|
12.5%
1/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/9 • From drug administration until end of trial examination, 5 days
|
0.00%
0/7 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
|
Metabolism and nutrition disorders
Erythema
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/9 • From drug administration until end of trial examination, 5 days
|
14.3%
1/7 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
0.00%
0/9 • From drug administration until end of trial examination, 5 days
|
14.3%
1/7 • From drug administration until end of trial examination, 5 days
|
0.00%
0/8 • From drug administration until end of trial examination, 5 days
|
12.5%
1/8 • From drug administration until end of trial examination, 5 days
|
Additional Information
Boehringer Ingelheim Call Center
Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.
- Publication restrictions are in place
Restriction type: OTHER