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

Liver Cirrhosis Clinical Trial

Official 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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05741372
• Other study ID #: 0352-2189
• Status: Recruiting
• Phase: N/A
• Start date: April 25, 2023
• Est. completion date: January 27, 2025

Study information

• Verified date: February 2024
• Source: Boehringer Ingelheim
• Contact: Boehringer Ingelheim
• Phone: 1-800-243-0127
• Email: clintriage.rdg[@]boehringer-ingelheim.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main trial objective, is to ascertain whether the transport activity, given by the maximum concentration (Cmax) and the area under the curve (AUC0-24) values for the different components in the transporter cocktail are similar or different in F4 liver cirrhosis patients on standard therapy compared to healthy subjects.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: January 27, 2025
• Est. primary completion date: January 14, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis

Intervention

Drug:
• Rosuvastatin
Rosuvastatin
• Digoxin
Digoxin
• Metformin hydrochlorid
Metformin hydrochloride
• Furosemide
Furosemide

Locations

Country	Name	City	State
Germany	CRS Clinical Research Services Mannheim GmbH	Mannheim

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 hours) for each component of the transporter cocktail: digoxin, furosemide, metformin, and rosuvastatin (AUC0-24)		Up to 24 hours
Primary	Maximum measured concentration of the analyte in plasma) for each component of the transporter cocktail: digoxin, furosemide, metformin, and rosuvastatin (Cmax)		Up to 24 hours

External Links

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