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

Not Applicable

Completed

• Conditions: Liver Cirrhosis
• Interventions: Drug: Caffeine; Drug: Warfarin sodium; Drug: Omeprazole; Drug: Metoprolol; Drug: Midazolam

• Registration Number: NCT05741385
• Lead Sponsor: Boehringer Ingelheim

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-02-14
• Study First Submitted QC: 2023-02-14
• Study First Posted: 2023-02-23
• Study Start: 2023-10-10
• Primary Completion: 2024-08-09
• Study Completion: 2024-08-23
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-13
• Last Update Posted: 2025-01-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 1: Healthy participants	Midazolam	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Group 1: Healthy participants	Warfarin sodium	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Group 1: Healthy participants	Caffeine	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Group 1: Healthy participants	Omeprazole	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Group 1: Healthy participants	Metoprolol	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam.
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)	Caffeine	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)	Warfarin sodium	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)	Metoprolol	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)	Omeprazole	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Group 2: F4 Child-Turcotte-Pugh class A (Child-Pugh A) participants (compensated)	Midazolam	Every participant receives a cocktail of Caffeine, Warfarin sodium, Omeprazole, Metoprolol, Midazolam. Compensated=without any disease symptoms
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)	Warfarin sodium	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
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)	Caffeine	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
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)	Omeprazole	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
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)	Metoprolol	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
Group 3: F4 Child-Turcotte-Pugh class B (Child-Pugh B) participants (decompensated)	Midazolam	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

Primary Outcome Measures

Name	Time	Method
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	Up to 108 hours
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	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)	Up to 108 hours

Trial Locations

Locations (1)

CRS Clinical Research Services Mannheim GmbH; 🇩🇪 Mannheim, Germany