Trial Outcomes & Findings for A Study to Compare How Different Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Handled by the Body of Healthy People and People With Liver Cirrhosis (NCT NCT05741372)
NCT ID: NCT05741372
Last Updated: 2026-01-13
Results Overview
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
28 participants
Primary outcome timeframe
Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.
Results posted on
2026-01-13
Participant Flow
The purpose of this single dose, open label study was to investigate whether the maximum concentration (Cmax) and the area under the concentration-time curve of the analyte in plasma from time point 0 to time point 24 hours (AUC0-24) values for the different components in the transporter cocktail - digoxin, furosemide, metformin and rosuvastatin are similar or different in F4 graded liver fibrosis (cirrhosis) patients on standard therapy compared to healthy participants.
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
Participant milestones
| Measure |
Group 1: Healthy Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Overall Study
STARTED
|
11
|
11
|
6
|
|
Overall Study
COMPLETED
|
11
|
11
|
6
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Study to Compare How Different Medicines (Rosuvastatin, Digoxin, Metformin, and Furosemide) Are Handled by the Body of Healthy People and People With Liver Cirrhosis
Baseline characteristics by cohort
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
Total
n=28 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
58.5 Years
STANDARD_DEVIATION 8.9 • n=9 Participants
|
60.2 Years
STANDARD_DEVIATION 11.9 • n=6 Participants
|
61.2 Years
STANDARD_DEVIATION 13.5 • n=9 Participants
|
59.7 Years
STANDARD_DEVIATION 10.8 • n=205 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=9 Participants
|
6 Participants
n=6 Participants
|
2 Participants
n=9 Participants
|
14 Participants
n=205 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=9 Participants
|
5 Participants
n=6 Participants
|
4 Participants
n=9 Participants
|
14 Participants
n=205 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=9 Participants
|
11 Participants
n=6 Participants
|
6 Participants
n=9 Participants
|
28 Participants
n=205 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
White
|
11 Participants
n=9 Participants
|
11 Participants
n=6 Participants
|
6 Participants
n=9 Participants
|
28 Participants
n=205 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=9 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=9 Participants
|
0 Participants
n=205 Participants
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
|
94.5 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.18
|
120.2 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.18
|
704.6 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.25
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax)
|
9.8 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.20
|
17.9 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.20
|
167.1 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.28
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Area Under the Concentration Time Curve of Digoxin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
|
8.1 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.08
|
7.8 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.08
|
7.6 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.10
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Maximum Measured Concentration of Digoxin in Plasma (Cmax)
|
1.7 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.09
|
1.3 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.09
|
1.4 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.13
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Area Under the Concentration Time Curve of Metformin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
|
2035.7 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.07
|
1982.8 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.07
|
1917.9 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.09
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Maximum Measured Concentration of Metformin in Plasma (Cmax)
|
348.0 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.07
|
303.6 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.07
|
291.0 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.10
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Area Under the Concentration Time Curve of Furosemide in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
|
238.0 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.09
|
210.1 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.09
|
275.0 hours*nanomole/liters (h*nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.12
|
PRIMARY outcome
Timeframe: Within 2 hours (hrs) before and at 30 minutes (min), 1 hrs, 1.5 hrs, 2 hrs, 3 hrs, 4 hrs, 6 hrs, 8 hrs, 10 hrs, 12 hrs, and 24 hrs after drug administration.Population: Pharmacokinetic parameter analysis set (PKS): This set included all subjects in the treated set (TS) who provided at least one pharmacokinetics (PK) endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability. Descriptive and model-based analyses of PK parameters were based on the PKS.
Adjusted geometric means and adjusted geometric standard errors were calculated using an analysis of variance (ANOVA) model on the logarithmic scale. The pharmacokinetics endpoint was log transformed (natural logarithm) prior to fitting the ANOVA model. This model included effects accounting for the following sources of variation: 'group', age, and BMI. All effects were considered as fixed.
Outcome measures
| Measure |
Group 1: Healthy Participants
n=11 Participants
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 Participants
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 Participants
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Maximum Measured Concentration of Furosemide in Plasma (Cmax)
|
81.1 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.10
|
62.3 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.10
|
78.0 nanomole/liters (nmol/l)
Standard Error NA
NA = adjusted geometric standard error = 1.14
|
Adverse Events
Group 1: Healthy Participants
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1: Healthy Participants
n=11 participants at risk
Healthy participants received a single dose of the following cocktail on Day 1 after a standardized light breakfast and 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
|
Group 2: F4 Child-Turcotte-Pugh Class A (Child-Pugh A) Subjects (Compensated)
n=11 participants at risk
Patients with compensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that meets the criteria for Child-Pugh A received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Compensated=without any disease symptoms
|
Group 3: F4 Child-Turcotte-Pugh Class B (Child-Pugh B) Subjects (Decompensated)
n=6 participants at risk
Patients with decompensated liver cirrhosis due to any underlying liver disease with advanced fibrosis (F4) and hepatic impairment that met the criteria for Child-Pugh B received a single dose of the following cocktail on Day 1 after a standardized light breakfast and with 280 ml of water: 0.25 milligrams (mg) digoxin as tablet, 1 mg furosemide as 0.1 milliliters (ml) oral solution, 10 mg metformin hydrochloride as 0.05 ml oral solution and 10 mg rosuvastatin as film-coated tablet.
Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
18.2%
2/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
18.2%
2/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/6 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
|
Nervous system disorders
Taste disorder
|
0.00%
0/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
9.1%
1/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/6 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
|
Gastrointestinal disorders
Diarrhoea
|
9.1%
1/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/6 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
|
Infections and infestations
Nasopharyngitis
|
9.1%
1/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/11 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
0.00%
0/6 • For AEs on-treatment period: From start of drug administration on Day 1 plus longest residual effect period for drugs in the cocktail, up to 10 days. For all-cause mortality: From start of drug administration until end of follow-up, up to 18 days.
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug. The treated set was used for safety analyses.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Phone: 1-800-243-0127
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER