Trial Outcomes & Findings for 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 (NCT NCT05741385)
NCT ID: NCT05741385
Last Updated: 2025-09-10
Results Overview
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.
COMPLETED
NA
4 participants
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.
2025-09-10
Participant Flow
The study aimed to investigate whether the metabolic activity of selected CYP isozymes differs between F4 liver cirrhosis patients receiving standard therapy and healthy subjects. It was planned that 12 healthy subjects, 12 compensated F4 Child-Pugh A patients and a minimum of 6 decompensated Child-Pugh B patients following clinical confirmation enter the study. Due to insufficient enrollment only 4 patients, all from Child-Pugh A cohort, were entered into the trial.
All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated
Participant milestones
| Measure |
Child-Pugh A
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Overall Study
STARTED
|
4
|
|
Overall Study
COMPLETED
|
4
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Age, Continuous
|
66.8 Years
STANDARD_DEVIATION 7.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
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.
Outcome measures
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
Caffeine
|
20600 Hour*nanogram/milliliter
Geometric Coefficient of Variation 37.3
|
|
Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
Omeprazole
|
1520 Hour*nanogram/milliliter
Geometric Coefficient of Variation 164
|
|
Area Under the Concentration Time Curve of Caffeine, Omeprazole and Metoprolol in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
Metoprolol
|
287 Hour*nanogram/milliliter
Geometric Coefficient of Variation 71.1
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
Area under the concentration time curve of midazolam in plasma over the time interval from 0 to 24 hours (AUC0-24) is reported.
Outcome measures
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Area Under the Concentration Time Curve of Midazolam in Plasma Over the Time Interval From 0 to 24 Hours (AUC0-24)
|
31200 Hour*picogram/milliliter
Geometric Coefficient of Variation 51.1
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
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.
Outcome measures
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
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)
R-warfarin
|
11200 Hour*nanogram/milliliter
Geometric Coefficient of Variation 18.3
|
|
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)
S-warfarin
|
5350 Hour*nanogram/milliliter
Geometric Coefficient of Variation 24.7
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
Maximum measured concentration of caffeine, omeprazole, metoprolol, R-warfarin and S-warfarin in plasma (Cmax) is reported.
Outcome measures
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)
Caffeine
|
2650 Nanogram/milliliter
Geometric Coefficient of Variation 23.4
|
|
Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)
Omeprazole
|
487 Nanogram/milliliter
Geometric Coefficient of Variation 67.9
|
|
Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)
Metoprolol
|
73.9 Nanogram/milliliter
Geometric Coefficient of Variation 72.3
|
|
Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)
R-warfarin
|
225 Nanogram/milliliter
Geometric Coefficient of Variation 26.3
|
|
Maximum Measured Concentration of Caffeine, Omeprazole, Metoprolol, R-warfarin and S-warfarin in Plasma (Cmax)
S-warfarin
|
226 Nanogram/milliliter
Geometric Coefficient of Variation 26.8
|
PRIMARY outcome
Timeframe: 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.Population: Pharmacokinetic parameter analysis set (PKS): All subjects in the treated set (TS) who provide at least one PK endpoint that was defined as primary and was not excluded due to a protocol deviation relevant to the evaluation of PK or due to PK non-evaluability.
Maximum measured concentration of midazolam in plasma (Cmax) is reported.
Outcome measures
| Measure |
Child-Pugh A
n=4 Participants
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Maximum Measured Concentration of Midazolam in Plasma (Cmax)
|
9520 Picogram/milliliter
Geometric Coefficient of Variation 38.9
|
Adverse Events
Child-Pugh A
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Child-Pugh A
n=4 participants at risk
Patients with compensated liver cirrhosis and advanced fibrosis grade F4 and hepatic impairment that met the criteria for Child-Pugh A received a drug cocktail of caffeine, warfarin, omeprazole, metoprolol and midazolam.
The drug cocktail was given as single oral dose of 100 mg caffeine (2 tablets), 5 mg warfarin sodium (1 tablet), 20 mg omeprazole (1 tablet), 50 mg metoprolol (1 tablet) and 2 mg/mL oral solution midazolam, with 240 mL of water after a standardized breakfast on Day 1.
|
|---|---|
|
Cardiac disorders
Atrioventricular block first degree
|
25.0%
1/4 • Adverse events and all-cause mortality: From administration of drug cocktail plus residual effect period, up to 9 days.
Treated Set (TS): All subjects who signed informed consent and were treated with study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
25.0%
1/4 • Adverse events and all-cause mortality: From administration of drug cocktail plus residual effect period, up to 9 days.
Treated Set (TS): All subjects who signed informed consent and were treated with study drug.
|
Additional Information
Boehringer Ingelheim, Call Center
Boehringer Ingelheim
Results disclosure agreements
- Principal investigator is a sponsor employee Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights
- Publication restrictions are in place
Restriction type: OTHER