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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

Primary Purpose

Liver Cirrhosis

Status
Recruiting
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Caffeine
Warfarin sodium
Omeprazole
Metoprolol
Midazolam
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Liver Cirrhosis

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CRS Clinical Research Services Mannheim GmbHRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

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)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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
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)
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

Secondary Outcome Measures

Full Information

First Posted
February 14, 2023
Last Updated
July 11, 2023
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT05741385
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 25, 2023 (Actual)
Primary Completion Date
May 28, 2024 (Anticipated)
Study Completion Date
June 10, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cirrhosis

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group 1: Healthy participants
Arm Type
Experimental
Arm Description
Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Arm Title
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)
Arm Type
Experimental
Arm Description
Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Arm Title
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Caffeine
Intervention Description
Caffeine
Intervention Type
Drug
Intervention Name(s)
Warfarin sodium
Intervention Description
Warfarin sodium
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention Description
Omeprazole
Intervention Type
Drug
Intervention Name(s)
Metoprolol
Intervention Description
Metoprolol
Intervention Type
Drug
Intervention Name(s)
Midazolam
Intervention Description
Midazolam
Primary Outcome Measure Information:
Title
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
Title
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
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boehringer Ingelheim
Phone
1-800-243-0127
Email
clintriage.rdg@boehringer-ingelheim.com
Facility Information:
Facility Name
CRS Clinical Research Services Mannheim GmbH
City
Mannheim
ZIP/Postal Code
68167
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Phone
08007234742
Email
deutschland@bitrialsupport.com

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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
Links:
URL
http://www.mystudywindow.com
Description
Related Info

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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

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