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

January 22, 2024 updated by: Boehringer Ingelheim

Profiling Study for the Hepatic Cytochrome P450 (CYP) Isozymes CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A in Healthy Subjects and in Patients With Stage 4 (F4) Liver Fibrosis / Cirrhosis by the Combined Administration of the Probe Substrates (the Cocktail) Caffeine, Warfarin, Omeprazole, Metoprolol, and Midazolam

The main trial objective is to ascertain whether the metabolism activity of selected cytochrome (CYP) isozymes caffeine (CYP1A2 probe drug), S-warfarin (CYP2C9 probe drug), omeprazole (CYP2C19 probe drug), metopolol (CYP2D6 probe drug), and midazolam (CYP3A probe drug) are similar or different in F4 liver cirrhosis patients on standard therapy compared to healthy subjects.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

30

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria

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)
  • 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. Furthermore, patients can only be included into the trial a) if they are in constant specialist care at the timepoint of enrollment into the study and b) if they are willing to continue to be in specialist care after participation in the 0352.2190 study
  • further inclusion criteria apply

Exclusion criteria

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)
  • Patients receiving antiviral therapy at the time of inclusion into the trial
  • further exclusion criteria apply

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group 1: Healthy participants
Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Drug: Midazolam
Midazolam
Drug: Caffeine
Caffeine
Drug: Warfarin sodium
Warfarin sodium
Drug: Omeprazole
Omeprazole
Drug: Metoprolol
Metoprolol
Experimental: Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)

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

Compensated=without any disease symptoms
Drug: Midazolam
Midazolam
Drug: Caffeine
Caffeine
Drug: Warfarin sodium
Warfarin sodium
Drug: Omeprazole
Omeprazole
Drug: Metoprolol
Metoprolol
Experimental: Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Area under the concentration time curve of the analyte in plasma over the time interval from 0 to 24 hours (AUC0-24) for caffeine, omeprazole, metoprolol, and midazolam
Time Frame: Up to 108 hours
Up to 108 hours
Area under the concentration time curve of warfarin, R-warfarin and S-warfarin in plasma over the time interval from 0 to 96 hours (AUC0-96)
Time Frame: Up to 108 hours
Up to 108 hours
Maximum measured concentration of the analyte in plasma (Cmax) for each component of the CYP-cocktail: caffeine, R-warfarin, S-warfarin, omeprazole, metoprolol, and midazolam
Time Frame: Up to 108 hours
Up to 108 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 25, 2023

Primary Completion (Estimated)

January 14, 2025

Study Completion (Estimated)

January 27, 2025

Study Registration Dates

First Submitted

February 14, 2023

First Submitted That Met QC Criteria

February 14, 2023

First Posted (Actual)

February 23, 2023

Study Record Updates

Last Update Posted (Actual)

January 23, 2024

Last Update Submitted That Met QC Criteria

January 22, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0352-2190

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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