A Study to Compare How Different Substances (Caffeine, Warfarin, Omeprazole, Metoprolol, and Midazolam) Are Handled by the Body of Healthy People and People With Liver Cirrhosis

NCT05741385 | Completed Results

• 1 other identifier: 0352-2190
• Study Type: interventional
• Target: 4
• 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 caffeine, warfarin,omeprazole, metoprolol, and midazolam 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 caffeine, warfarin, omeprazole, metoprolol, and midazolam 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 5 times. For 1 of the visits, participants 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 (5)

• Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)

  Area under the concentration time curve of caffeine, omeprazole and metoprolol in plasma over the time interval from 0 to 24 hours (AUC0-24) is reported.

  2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration.

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

  Area under the concentration time curve of midazolam in plasma over the time interval from 0 to 24 hours (AUC0-24) is reported.

  2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration.

• Area Under the Concentration Time Curve of R-warfarin and S-warfarin in Plasma Over the Time Interval From 0 to 96 Hours (AUC0-96)

  Area under the concentration time curve of R-warfarin and S-warfarin in plasma over the time interval from 0 to 96 hours (AUC0-96) is reported.

  2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration.

• Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)

  Maximum measured concentration of caffeine, omeprazole, metoprolol, R-warfarin and S-warfarin in plasma (Cmax) is reported.

  2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration.

• Maximum Measured Concentration of Midazolam in Plasma (Cmax)

  Maximum measured concentration of midazolam in plasma (Cmax) is reported.

  2 hours before drug administration and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48-72 and 96 (+/-12) hours after drug administration.

Study Arms (3)

Group 1: Healthy participants

EXPERIMENTAL

Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.

Drug: Caffeine; Drug: Warfarin sodium; Drug: Omeprazole; Drug: Metoprolol; Drug: Midazolam

Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)

EXPERIMENTAL

Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms

Drug: Caffeine; Drug: Warfarin sodium; Drug: Omeprazole; Drug: Metoprolol; Drug: Midazolam

Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)

EXPERIMENTAL

Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Decompensated= with disease symptoms like aszites, variceal bleeding, hepatic encephalopathy, hepato-renal syndrome

Drug: Caffeine; Drug: Warfarin sodium; Drug: Omeprazole; Drug: Metoprolol; Drug: Midazolam

Interventions

Caffeine DRUG

Caffeine

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

Warfarin sodium DRUG

Warfarin sodium

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

Omeprazole DRUG

Omeprazole

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

Metoprolol DRUG

Metoprolol

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

Midazolam DRUG

Midazolam

Group 1: Healthy participants; Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated); Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (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 Harmonisation-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 vasectomised 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 sterilised (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 (except from caffeine: methylxanthine-containing drinks or foods such as coffee, tea, cola, energy drinks, or chocolate are not allowed within 48 hours (h) before and during the inhouse confinement at the trial site)
• 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

You may not qualify if:

• Healthy subjects and F4 liver cirrhosis patients:
• Subjects already taking any components in the cocktail within 4 weeks before cocktail administration (except from caffeine: methylxanthine-containing drinks or foods such as coffee, tea, cola, energy drinks, or chocolate are not allowed within 48 h before and during the in-house confinement at the trial site)
• Subjects with any other condition that would preclude administration of caffeine, warfarin, omeprazole, metoprolol, and midazolam (i.e., contraindicated as per Summary of Product Characteristics (SmPC)), such as hypersensitivity to active ingredient or any of the excipients or to any beta receptor blockers
• 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 50 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)

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

Caffeine; Warfarin; Omeprazole; Metoprolol; Midazolam

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 4-Hydroxycoumarins; Coumarins; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Benzimidazoles; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Propanols; Amines; Benzodiazepines; Benzazepines

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: October 10, 2023
• Primary Completion: August 9, 2024
• Study Completion: August 23, 2024
• Last Updated: September 10, 2025
• Results First Posted: September 10, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)