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Completed

NCT Number: NCT05741372

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

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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Key information

Conditions

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

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CRS Clinical Research Services Mannheim GmbH

Mannheim, 68167, Germany

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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:
  • 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)
  • Body mass index (BMI) of 18.5 to 35 kilograms per meter squared (kg/m2) (inclusive). A BMI of ≥ 30 is no exclusion criterion when the subject can be considered healthy apart from the elevated BMI
  • further inclusion criteria apply

F4 liver cirrhosis patients only:

  • Male and female subjects, 18 to 75 years
  • BMI of 18.5 to 40.0 kg/m2 (inclusive)
  • Stable treatment for at least 4 weeks prior to taking the cocktail
  • further inclusion criteria apply

Healthy subjects and F4 liver cirrhosis patients:

  • Subjects already taking digoxin, furosemide, metformin or rosuvastatin within 4 weeks of enrolment into the study. Furthermore, patients taking ezetimibe, fibrates, or the maximal dose (per Summary of Product Characteristics (SmPC)) of any statin are excluded from this study.
  • Subjects with any other condition that would preclude administration of digoxin, furosemide, metformin or rosuvastatin (i.e., contraindicated as per SmPC), such as hypersensitivity to active ingredient or any of the excipients or to sulphonamides, hypovolemia or dehydration, and partial obstructions of urinary outflow (e.g., prostatic hypertrophy)
  • Repeated measurement of systolic blood pressure outside the range of 90 to 150 millimeter of mercury (mmHg), diastolic blood pressure outside the range of 50 to 95 mmHg, or pulse rate outside the range of 60 to 90 beats per minute (bpm)
  • Cholecystectomy or other surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy or simple hernia repair)
  • Diseases of the central nervous system (including but not limited to any kind of seizures or stroke), and other relevant neurological or psychiatric disorders
  • History of relevant orthostatic hypotension, fainting spells, or blackouts
  • Relevant (other than Hepatitis B virus (HBV) or Hepatitis C virus (HCV)) chronic or acute infections (including an ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection)
  • Patients receiving antiviral therapy at the time of inclusion into the trial
  • further exclusion criteria apply

Treatment and study plan

Rosuvastatin

Drug

Rosuvastatin

Digoxin

Drug

Digoxin

Metformin hydrochlorid

Drug

Metformin hydrochloride

Furosemide

Drug

Furosemide

Primary outcomes

  1. Area Under the Concentration Time Curve of Rosuvastatin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)

    Time frame: 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.

    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.

  2. Maximum Measured Concentration of Rosuvastatin in Plasma (Cmax)

    Time frame: 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.

    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.

  3. Area Under the Concentration Time Curve of Digoxin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)

    Time frame: 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.

    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.

  4. Maximum Measured Concentration of Digoxin in Plasma (Cmax)

    Time frame: 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.

    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.

  5. Area Under the Concentration Time Curve of Metformin in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)

    Time frame: 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.

    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.

  6. Maximum Measured Concentration of Metformin in Plasma (Cmax)

    Time frame: 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.

    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.

  7. Area Under the Concentration Time Curve of Furosemide in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)

    Time frame: 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.

    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.

  8. Maximum Measured Concentration of Furosemide in Plasma (Cmax)

    Time frame: 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.

    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.

Sponsors and collaborators

Lead sponsor

Boehringer Ingelheim

Industry

Registry information

Official study title

Transporter Profiling Study for P-glycoprotein 1 (P-gp), Organic Anion Transporter 1 (OAT1), Organic Anion Transporter 3 (OAT3), Organic Cation Transporter 2 (OCT2), Multidrug and Toxin Extrusion Protein 1 (MATE1), Multidrug and Toxin Extrusion Protein 2-K (MATE2-K), Organic Anion Transporting Polypeptide 1B1 (OATP1B1), Organic Anion Transporting Polypeptide 1B3 (OATP1B3) and Breast Cancer Resistance Protein (BCRP) in Healthy Subjects and in Patients With Stage 4 (F4) Liver Fibrosis / Cirrhosis.

Important dates

Study start
2023
Primary completion
2024
Study completion
2024
First posted
Feb 23, 2023
Registry last updated
Jan 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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