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Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of BI 10773 in Type II Diabetes Patients With Different Degrees of Renal Impairment

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ClinicalTrials.gov Identifier: NCT01907113
Recruitment Status : Completed
First Posted : July 24, 2013
Results First Posted : July 14, 2014
Last Update Posted : July 14, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Diabetes Mellitus, Type 2
Intervention Drug: BI 10773
Enrollment 40
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.

Pre-assignment Details  
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description

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.

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.

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.

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.

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.
Period Title: Overall Study
Started 8 9 7 8 8
Completed 8 9 7 8 8
Not Completed 0 0 0 0 0
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure Total
Hide Arm/Group Description

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.

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.

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.

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.

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 of all reporting groups
Overall Number of Baseline Participants 8 9 7 8 8 40
Hide Baseline Analysis Population Description
The treated set included all patients who were dispensed study medication and were documented to have at least one dose of investigational treatment.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 8 participants 9 participants 7 participants 8 participants 8 participants 40 participants
54.5  (11.7) 60.0  (8.8) 63.1  (9.5) 56.0  (12.9) 45.8  (12.0) 55.8  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8 participants 9 participants 7 participants 8 participants 8 participants 40 participants
Female
7
  87.5%
6
  66.7%
3
  42.9%
1
  12.5%
4
  50.0%
21
  52.5%
Male
1
  12.5%
3
  33.3%
4
  57.1%
7
  87.5%
4
  50.0%
19
  47.5%
1.Primary Outcome
Title AUC0-∞ (Area Under the Concentration Time Curve of the Analyte in Plasma Over the Time Interval From 0 to Infinity)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
10500
(17.6%)
12400
(21.6%)
12600
(27.1%)
17500
(18.9%)
15600
(38.6%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Mild Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as mild renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 118.24
Confidence Interval (2-Sided) 90%
96.17 to 145.38
Parameter Dispersion
Type: Standard Deviation
Value: 25.6
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Moderate Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as moderate renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 119.94
Confidence Interval (2-Sided) 90%
96.25 to 149.47
Parameter Dispersion
Type: Standard Deviation
Value: 25.6
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Severe Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as severe renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 166.29
Confidence Interval (2-Sided) 90%
134.44 to 205.68
Parameter Dispersion
Type: Standard Deviation
Value: 25.6
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Kidney Failure
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as kidney failure divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 148.29
Confidence Interval (2-Sided) 90%
119.89 to 183.42
Parameter Dispersion
Type: Standard Deviation
Value: 25.6
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
2.Primary Outcome
Title Cmax (Maximum Concentration of the Analyte in Plasma)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol/L
1210
(24.1%)
1430
(33.1%)
1230
(30.9%)
1450
(33.0%)
1250
(25.9%)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Mild Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as mild renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 118.83
Confidence Interval (2-Sided) 90%
93.62 to 150.84
Parameter Dispersion
Type: Standard Deviation
Value: 29.7
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Moderate Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as moderate renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 102.27
Confidence Interval (2-Sided) 90%
79.33 to 131.85
Parameter Dispersion
Type: Standard Deviation
Value: 29.7
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Severe Renal Impairment
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as severe renal function divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 120.68
Confidence Interval (2-Sided) 90%
94.42 to 154.25
Parameter Dispersion
Type: Standard Deviation
Value: 29.7
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Normal Renal Function, Kidney Failure
Comments No formal testing, investigation of relative bioavailability
Type of Statistical Test Non-Inferiority or Equivalence
Comments Ratio calculated as kidney failure divided by normal renal function
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments Based on ANOVA with fixed effect for treatment (corresponding to renal impairment status).
Method of Estimation Estimation Parameter Geometric mean ratio
Estimated Value 103.75
Confidence Interval (2-Sided) 95%
81.18 to 132.61
Parameter Dispersion
Type: Standard Deviation
Value: 29.7
Estimation Comments Standard deviation is actually the geometric Coefficient of Variation [%].
3.Secondary Outcome
Title Time to Maximum Concentration of the Analyte in Plasma
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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Median (Full Range)
Unit of Measure: h
1.00
(1.00 to 3.00)
2.50
(2.00 to 4.00)
2.00
(1.50 to 3.00)
2.00
(0.67 to 4.00)
2.50
(1.50 to 3.00)
4.Secondary Outcome
Title Half-life and Mean Residence Time of the Analyte in Plasma
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h
Terminal half-life
17.4
(57.4%)
19.3
(81.6%)
19.5
(63.9%)
22.5
(74.3%)
18.5
(62.6%)
Mean residence time
13.1
(37.4%)
15.7
(44.6%)
18.4
(52.7%)
22.2
(57.6%)
19.8
(51.2%)
5.Secondary Outcome
Title Terminal Rate Constant in Plasma
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: 1/h
0.0398
(57.4%)
0.0360
(81.6%)
0.0355
(63.9%)
0.0308
(74.3%)
0.0375
(62.6%)
6.Secondary Outcome
Title Apparent Clearance of the Analyte in the Plasma After Extravascular Administration
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/min
176
(17.6%)
149
(21.6%)
147
(27.1%)
106
(18.9%)
119
(38.6%)
7.Secondary Outcome
Title Apparent Volume of Distribution During the Terminal Phase Lz
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: L
266
(55.1%)
248
(76.3%)
248
(55.5%)
206
(78.0%)
190
(45.1%)
8.Secondary Outcome
Title 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)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol*h/L
10300
(17.5%)
12100
(20.9%)
12100
(24.4%)
16500
(19.9%)
14900
(34.4%)
9.Secondary Outcome
Title Ae0-96 (Amount of Analyte That is Eliminated in Urine Over the Time Interval 0 to 96 h)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nmol
17300
(26.1%)
12100
(43.8%)
6840
(85.5%)
3730
(49.3%)
300
(117%)
10.Secondary Outcome
Title fe0-96 (Fraction of Analyte Excreted Unchanged in Urine From Time Points 0 to 96 Hours)
Hide Description 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
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PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percentage of analyte
15.6
(26.1%)
10.9
(43.8%)
6.16
(85.5%)
3.36
(49.3%)
0.271
(117%)
11.Secondary Outcome
Title Renal Clearance of the Analyte in Plasma After Extravascular Administration
Hide Description 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
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Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 5
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: mL/min
28.0
(19.5%)
16.7
(53.7%)
9.39
(87.9%)
3.70
(38.5%)
0.349
(188%)
12.Secondary Outcome
Title %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)
Hide Description 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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: percent
0.869
(225%)
1.07
(243%)
1.21
(223%)
1.78
(334%)
1.14
(330%)
13.Secondary Outcome
Title Plasma Protein Binding
Hide Description

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
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
PKS
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 8 8 8 8
Mean (Standard Deviation)
Unit of Measure: percentage of plasma protein binding
Pre-dose 83.61  (1.10) 82.72  (3.36) 81.29  (2.48) 79.98  (2.42) 81.08  (1.54)
1:30 h after dosing 85.18  (1.91) 83.70  (2.49) 82.68  (2.76) 81.02  (1.73) 81.09  (1.94)
3:00 h after dosing 83.94  (1.88) 83.18  (2.58) 81.90  (1.69) 80.38  (1.61) 80.32  (2.00)
14.Secondary Outcome
Title Total Urinary Glucose Excretion (UGE)
Hide Description 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)
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Hide Analysis Population Description
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/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 7 5 6 5
Mean (Standard Error)
Unit of Measure: mg
97643  (7204) 61590  (6892) 55674  (16891) 18251  (3925) 779  (904)
15.Secondary Outcome
Title Safety: Physical Examination, Vital Signs, ECG and Laboratory Measurements
Hide Description 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
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Hide Analysis Population Description
Treated set
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Measure Type: Number
Unit of Measure: participants
Physical examination 0 0 0 0 0
Vital signs 0 0 0 0 0
ECG 0 0 0 0 0
Laboratory Measurements 0 0 0 0 0
16.Secondary Outcome
Title Assessment of Tolerability by Investigator
Hide Description 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
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Treated set
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description:

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.

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.

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.

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.

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 Number of Participants Analyzed 8 9 7 8 8
Measure Type: Number
Unit of Measure: participants
Good 8 9 7 8 8
Satisfactory 0 0 0 0 0
Not satisfactory 0 0 0 0 0
Bad 0 0 0 0 0
Not assessable 0 0 0 0 0
Time Frame From drug administration until end of trial examination, 5 days
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Hide Arm/Group Description

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.

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.

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.

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.

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.
All-Cause Mortality
Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/8 (0.00%)   0/9 (0.00%)   0/7 (0.00%)   0/8 (0.00%)   0/8 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Normal Renal Function Mild Renal Impairment Moderate Renal Impairment Severe Renal Impairment Kidney Failure
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/8 (12.50%)   0/9 (0.00%)   1/7 (14.29%)   0/8 (0.00%)   2/8 (25.00%) 
Gastrointestinal disorders           
Diarrhoea  1  0/8 (0.00%)  0/9 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nausea  1  1/8 (12.50%)  0/9 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Metabolism and nutrition disorders           
Erythema  1  0/8 (0.00%)  0/9 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  0/8 (0.00%) 
Nervous system disorders           
Headache  1  1/8 (12.50%)  0/9 (0.00%)  0/7 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders           
Pruritus  1  0/8 (0.00%)  0/9 (0.00%)  1/7 (14.29%)  0/8 (0.00%)  1/8 (12.50%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MEDDRA 12.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim Pharmaceuticals
Phone: 1-800-243-0127
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01907113     History of Changes
Other Study ID Numbers: 1245.12
2008-006086-86 ( EudraCT Number: EudraCT )
First Submitted: July 15, 2013
First Posted: July 24, 2013
Results First Submitted: May 16, 2014
Results First Posted: July 14, 2014
Last Update Posted: July 14, 2014