Trial Outcomes & Findings for Pharmacokinetics of Empagliflozin (BI 10773) in Patients With Impaired Liver Function (NCT NCT01111318)

NCT ID: NCT01111318

Last Updated: 2014-06-13

Results Overview

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity. The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 36 participants
• Primary outcome timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration
• Results posted on: 2014-06-13

Participant Flow

Participant milestones

Measure	Healthy Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Overall Study STARTED	12	8	8	8
Overall Study COMPLETED	12	8	8	8
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Pharmacokinetics of Empagliflozin (BI 10773) in Patients With Impaired Liver Function

Baseline characteristics by cohort

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.	Total n=36 Participants Total of all reporting groups
Age, Continuous	53.8 years STANDARD_DEVIATION 9.2 • n=5 Participants	57.0 years STANDARD_DEVIATION 6.9 • n=7 Participants	51.0 years STANDARD_DEVIATION 8.5 • n=5 Participants	53.9 years STANDARD_DEVIATION 9.6 • n=4 Participants	53.9 years STANDARD_DEVIATION 8.6 • n=21 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	4 Participants n=4 Participants	19 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants	4 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 extrapolated to infinity.

The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Area Under the Curve 0 to Infinity (AUC0-∞)	10800 nmol*h/L Standard Deviation 22.6	13800 nmol*h/L Standard Deviation 38.6	16100 nmol*h/L Standard Deviation 26.2	19000 nmol*h/L Standard Deviation 27.1

PRIMARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Maximum measured concentration of empagliflozin (empa) in plasma.

The standard deviation is actually the coefficient of variation. The 'measured values' show inter-individual variabilities, whereas the statistical analyses show intra-individual variabilities.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Maximum Measured Concentration (Cmax)	1370 nmol/L Standard Deviation 33.9	1430 nmol/L Standard Deviation 36.8	1660 nmol/L Standard Deviation 26.4	1970 nmol/L Standard Deviation 22.1

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration.

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Area under the concentration-time curve of empagliflozin (empa) in plasma over the time interval from 0 to the time of the last quantifiable data point.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Area Under the Curve 0 to Time of Last Quantifiable Data Point (AUC0-tz)	10700 nmol*h/L Standard Deviation 22.6	13700 nmol*h/L Standard Deviation 38.4	15800 nmol*h/L Standard Deviation 25.7	18600 nmol*h/L Standard Deviation 23.9

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration.

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Time from dosing to maximum concentration of empagliflozin (empa) in plasma.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Time From Dosing to Maximum Concentration (Tmax)	2.00 h Full Range 50.1 • Interval 1.0 to 4.0	1.50 h Full Range 73.2 • Interval 0.67 to 4.0	2.00 h Full Range 64.4 • Interval 0.67 to 2.5	1.50 h Full Range 48.2 • Interval 0.67 to 2.5

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Terminal rate constant in plasma.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Terminal Rate Constant (λz)	0.0414 1/h Standard Deviation 41.6	0.0404 1/h Standard Deviation 23.5	0.0454 1/h Standard Deviation 28.9	0.0506 1/h Standard Deviation 41.1

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Terminal half-life of empagliflozin (empa) in plasma.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Terminal Half-Life (t1/2)	19.9 h Standard Deviation 43.1	18.1 h Standard Deviation 25.9	17.1 h Standard Deviation 45.9	17.7 h Standard Deviation 67.4

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Mean residence time of empagliflozin (empa) in the body.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Mean Residence Time (MRTpo)	13.2 h Standard Deviation 31.3	14.4 h Standard Deviation 22.9	15.5 h Standard Deviation 37.2	15.7 h Standard Deviation 43.0

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Apparent clearance of empagliflozin (empa) in the plasma after extravascular administration.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Apparent Clearance After Extravascular Administration (CL/F)	179 mL/min Standard Deviation 23.9	150 mL/min Standard Deviation 34.4	124 mL/min Standard Deviation 30.7	103 mL/min Standard Deviation 23.0

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Apparent volume of distribution during the terminal phase (λz).

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Apparent Volume of Distribution During the Terminal Phase (Vz/F)	298 L Standard Deviation 39.5	237 L Standard Deviation 45.5	173 L Standard Deviation 35.0	144 L Standard Deviation 46.7

SECONDARY outcome

Timeframe: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Amount of empagliflozin (empa) that is eliminated in urine over the time interval 0 to 96 hours.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Amount of Empagliflozin That is Eliminated in Urine (Ae0-96)	18400 nmol Standard Deviation 26.5	16900 nmol Standard Deviation 20.6	18500 nmol Standard Deviation 35.0	22500 nmol Standard Deviation 23.5

SECONDARY outcome

Timeframe: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Fraction of empagliflozin (empa) excreted unchanged in urine from time points 0 to 96 hours.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Fraction of Empagliflozin Excreted Unchanged in Urine (fe0-96))	16.6 percentage of empagliflozin Standard Deviation 26.5	15.2 percentage of empagliflozin Standard Deviation 20.6	16.7 percentage of empagliflozin Standard Deviation 35.0	20.3 percentage of empagliflozin Standard Deviation 23.5

SECONDARY outcome

Timeframe: Pre-dose and 20minutes (min), 40min, 1h, 1.5h, 2h, 2.5h, 3h, 4h, 6h, 8h, 10h, 12h, 16h, 24h, 36h, 48h, 72h and 96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Renal clearance of empagliflozin (empa) in plasma after extravascular administration.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Renal Clearance After Extravascular Administration (CL R)	28.7 mL/min Standard Deviation 30.3	23.7 mL/min Standard Deviation 48.0	19.9 mL/min Standard Deviation 36.8	21.3 mL/min Standard Deviation 37.1

SECONDARY outcome

Timeframe: Pre-dose and time intervals 0-4h, 4-8h, 8-12h, 12-24h, 24-36h, 36-48h, 48-72h and 72-96h after drug administration

Population: Pharmacokinetic (PK) set included all subjects who were documented to have taken the investigational treatment, who provided at least one observation for at least one primary PK endpoint, without important protocol violations relevant to the evaluation of PK, provided no vomiting occurred at or before two times median tmax.

Urinary glucose excretion, this endpoint was measured using Ae0-96.

The standard deviation is actually the coefficient of variation.

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=7 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Urinary Glucose Excretion (UGE)	86600 mg Standard Deviation 34.8	81000 mg Standard Deviation 26.7	79700 mg Standard Deviation 67.9	79800 mg Standard Deviation 45.6

SECONDARY outcome

Timeframe: Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days

Population: Treated Set (TS) included all subjects who had been dispensed study medication and were documented to have taken the investigational treatment.

Clinically relevant abnormalities for physical examination, vital signs, ECG, clinical laboratory tests and assessment of tolerability by the investigator. New abnormal findings or worsening of baseline conditions were reported as Adverse Events (AE).

Outcome measures

Measure	Healthy n=12 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 Participants Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator Investigations: Electrocardiogram abnormal	2 participants	0 participants	0 participants	0 participants
Clinically Relevant Abnormalities for Physical Examination, Vital Signs, ECG, Clinical Laboratory Tests and Assessment of Tolerability by the Investigator Investigations: Nitrite urine present	0 participants	0 participants	0 participants	1 participants

Adverse Events

Healthy

Serious events: 0 serious events

Other events: 6 other events

Deaths: 0 deaths

Mild

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Moderate

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Severe

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	Healthy n=12 participants at risk Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for healthy subjects with normal liver function who matched the hepatically impaired subjects with regard to age and weight.	Mild n=8 participants at risk Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with mild liver impairment defined by Child-Pugh class A.	Moderate n=8 participants at risk Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with moderate liver impairment defined by Child-Pugh class B.	Severe n=8 participants at risk Single oral dose of empagliflozin (empa) 50mg (2 tablets of 25mg) following an overnight fast, for patients with severe liver impairment defined by Child-Pugh class C.
Cardiac disorders Myocardial ischaemia	0.00% 0/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	25.0% 2/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Gastrointestinal disorders Constipation	33.3% 4/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Gastrointestinal disorders Toothache	8.3% 1/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
General disorders Pyrexia	0.00% 0/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Infections and infestations Asymptomatic bacteriuria	0.00% 0/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Investigations Electrocardiogram abnormal	16.7% 2/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Investigations Nitrite urine present	0.00% 0/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Musculoskeletal and connective tissue disorders Back pain	8.3% 1/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Nervous system disorders Headache	25.0% 3/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days
Renal and urinary disorders Leukocyturia	0.00% 0/12 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	0.00% 0/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days	12.5% 1/8 • Drug administration until 4 days after drug administration or end-of-study visit, up to 19 days

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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