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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-514621-29-00 | Registry Identifier | CTIS |
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This study is open to healthy adults and adults with liver cirrhosis. The purpose of this study is to compare how different medicines are handled by the body in people with and without liver cirrhosis. The study measures if the approved medicines rosuvastatin, digoxin, metformin, and furosemide are processed differently in people with liver cirrhosis than in people without liver cirrhosis.
This study will help to understand how new medicines being developed are handled by the body in people with liver cirrhosis. There are 3 groups in this study: people without liver cirrhosis, people with mild liver cirrhosis, and people with moderate liver cirrhosis. All participants get 1 dose each of rosuvastatin, digoxin, metformin, and furosemide by mouth. The participants with liver cirrhosis continue their regular treatment for the condition during the study.
Participants are in the study for about 1 month. During this time, they visit the study site 4 times. For 1 of the visits, they stay overnight for 2 nights at the study site. To assess the main study endpoint, the doctors take frequent blood samples from the participants. The doctors also regularly check participants' health and take note of any unwanted effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1: Healthy participants | Experimental | 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) | Experimental | 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) | Experimental | 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 |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rosuvastatin | Drug | Rosuvastatin |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. |
| Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax) | 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. | 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. |
| Area Under the Concentration Time Curve of Digoxin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. |
| Maximum Measured Concentration of Digoxin in Plasma (Cmax) |
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Inclusion criteria
Healthy subjects and F4 liver cirrhosis patients:
Signed and dated written informed consent in accordance with the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial
Either male subject, or female subject who meets any of the following criteria for a highly effective contraception from at least 30 days before the first administration of trial medication until 30 days after trial completion:
Healthy subjects only:
F4 liver cirrhosis patients only:
Healthy subjects and F4 liver cirrhosis patients:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CRS Clinical Research Services Mannheim GmbH | Mannheim | 68167 | Germany |
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| Label | URL |
|---|---|
| Related Info | View source |
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Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents. Exceptions might apply, e.g., studies in products where Boehringer Ingelheim is not the license holder; studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; studies conducted in a single center or targeting rare diseases (in case of low number of patients and therefore limitations with anonymization). For more details refer to: https:// www.mystudywindow.com/msw/datatransparency
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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.
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 9, 2023 | Dec 4, 2025 |
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|
| Digoxin | Drug | Digoxin |
|
| Metformin hydrochlorid | Drug | Metformin hydrochloride |
|
| Furosemide | Drug | Furosemide |
|
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.
| 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. |
| Area Under the Concentration Time Curve of Metformin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. |
| Maximum Measured Concentration of Metformin in Plasma (Cmax) | 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. | 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. |
| Area Under the Concentration Time Curve of Furosemide in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. |
| Maximum Measured Concentration of Furosemide in Plasma (Cmax) | 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. | 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. |
| FG001 |
| 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 |
| FG002 | 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 |
| COMPLETED |
|
| NOT COMPLETED |
|
Treated set (TS): The treated set included all subjects who signed informed consent and were treated with at least one dose of study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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 |
| BG002 | 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 |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | hours*nanomole/liters (h*nmol/l) | 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. |
|
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| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liters (nmol/l) | 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. |
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| Primary | Area Under the Concentration Time Curve of Digoxin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | hours*nanomole/liters (h*nmol/l) | 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. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Maximum Measured Concentration of Digoxin in Plasma (Cmax) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liters (nmol/l) | 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. |
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| Primary | Area Under the Concentration Time Curve of Metformin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | hours*nanomole/liters (h*nmol/l) | 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. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Maximum Measured Concentration of Metformin in Plasma (Cmax) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liters (nmol/l) | 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. |
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| Primary | Area Under the Concentration Time Curve of Furosemide in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | hours*nanomole/liters (h*nmol/l) | 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. |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Maximum Measured Concentration of Furosemide in Plasma (Cmax) | 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. | 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. | Posted | Geometric Least Squares Mean | Standard Error | nanomole/liters (nmol/l) | 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. |
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. | 0 | 11 | 0 | 11 | 3 | 11 |
| EG001 | 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 | 0 | 11 | 0 | 11 | 3 | 11 |
| EG002 | 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 | 0 | 6 | 0 | 6 | 0 | 6 |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Taste disorder | Nervous system disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 27.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 27.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim, Call Center | Boehringer Ingelheim | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 17, 2025 | Dec 4, 2025 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008103 | Liver Cirrhosis |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D005355 | Fibrosis |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| D000068718 | Rosuvastatin Calcium |
| D004077 | Digoxin |
| D005665 | Furosemide |
| ID | Term |
|---|---|
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D005464 | Fluorobenzenes |
| D006845 | Hydrocarbons, Fluorinated |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D004071 | Digitalis Glycosides |
| D002298 | Cardenolides |
| D002301 | Cardiac Glycosides |
| D002297 | Cardanolides |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
| D013424 | Sulfanilamides |
| D000814 | Aniline Compounds |
| D000588 | Amines |
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
The adjusted geometric means ratio based on ANOVA was calculated by using least square means, the 90% CI by using residual error from quantiles from t-distribution. These quantities were back-transformed to original scale. |
| Adjusted geometric mean ratio |
| 745.7 |
| 2-Sided |
| 90 |
| 464.9 |
| 1196 |
Ratio [%]=(adjusted geometric mean Group 3/adjusted geometric mean Group 1)*100. Total gCV = 28.1%. |
| Other |
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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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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: O.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 |
| OG002 | 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: O.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 |
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