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

NCT05741372 | Completed Results

• 2 other identifiers: 0352-21892024-514621-29-00
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Liver Cirrhosis

Outcome Measures

Primary Outcomes (8)

• 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)

  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.

Study Arms (3)

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.

Drug: Rosuvastatin; Drug: Digoxin; Drug: Metformin hydrochlorid; Drug: Furosemide

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

Drug: Rosuvastatin; Drug: Digoxin; Drug: Metformin hydrochlorid; Drug: Furosemide

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

Drug: Rosuvastatin; Drug: Digoxin; Drug: Metformin hydrochlorid; Drug: Furosemide

Interventions

Furosemide DRUG

Furosemide

Group 1: Healthy participants; Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) subjects (compensated); Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) subjects (decompensated)

Rosuvastatin DRUG

Rosuvastatin

Group 1: Healthy participants; Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) subjects (compensated); Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) subjects (decompensated)

Digoxin DRUG

Digoxin

Group 1: Healthy participants; Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) subjects (compensated); Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) subjects (decompensated)

Metformin hydrochlorid DRUG

Metformin hydrochloride

Group 1: Healthy participants; Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) subjects (compensated); Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) subjects (decompensated)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Use of combined (estrogen and progestogen containing) hormonal contraception that prevents ovulation (oral, intravaginal, or transdermal), plus condom
• Use of progestogen-only hormonal contraception that inhibits ovulation (only injectables or implants), plus condom
• Use of intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
• Sexually abstinent
• A vasectomized sexual partner who received medical assessment of the surgical success (documented absence of sperm) and provided that the partner is the sole sexual partner of the trial participant
• Surgically sterilized (including hysterectomy)
• Postmenopausal, defined as no menses for 1 year without an alternative medical cause (in questionable cases a blood sample with levels of follicle-stimulating hormone (FSH) above 40 units per liter (U/L) and estradiol below 30 nanograms per liter (ng/L) is confirmatory)
• Not taking any components in the cocktail within 4 weeks of enrolment
• Healthy subjects only:
• Healthy male or female subjects according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), and clinical laboratory tests
• Age of 18 to 75 years (inclusive)
• F4 liver cirrhosis patients only:

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (1)

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Location

Related Links

• Related Info

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

Rosuvastatin Calcium; Digoxin; Furosemide

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Sulfanilamides; Aniline Compounds; Amines

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: February 23, 2023
• Study Start: September 7, 2023
• Primary Completion: December 18, 2024
• Study Completion: December 30, 2024
• Last Updated: January 13, 2026
• Results First Posted: January 13, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)