Effect of BI 1181181 on Midazolam, Warfarin, Omeprazole and Digoxin

Study Overview
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Brief Summary
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To assess the influence of different dose strengths of BI 1181181 on single dose kinetics of midazolam (CYP3A4 probe drug), warfarin (CYP2C9 probe drug), omeprazole (CYP2C19 probe drug) and digoxin (P-gp probe drug)

Official Title
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A Study to Investigate the Effects of BI 1181181 on the Pharmacokinetics of Midazolam, Warfarin, Omeprazole and Digoxin in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: Omeprazole
* Drug: Warfarin
* Drug: BI 1181181
* Drug: Midazolam
* Drug: Omeprazole
* Drug: BI 1181181
* Drug: Midazolam
* Drug: Midazolam
* Drug: Warfarin
* Drug: BI 1181181
* Drug: Digoxin
* Drug: Digoxin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: healthy male subjects age of 18 to 50 years body mass index (BMI) of 18.5 to 29.9 kg/m2 Subjects must be able to understand and comply with study requirements Exclusion criteria: Any finding in the medical examination (including BP, PR or ECG) is deviating from normal and judged as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 50 to 90 bpm at screening Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease judged as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with the pharmacokinetics of the trial medication (except appendectomy and 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment 3<br>single dose of midazolam + BI drug | Drug: Midazolam<br> <br> Drug: BI 1181181<br> <br> |
| Experimental: Treatment 4<br>single dose of probe drugs + BI drug | Drug: Omeprazole<br> <br> Drug: Midazolam<br> <br> Drug: BI 1181181<br> <br> Drug: Warfarin<br> <br> |
| Experimental: Treatment 5<br>single dose of digoxin + BI drug | Drug: BI 1181181<br> <br> Drug: Digoxin<br> <br> |
| Experimental: Treatment 1<br>single doses of probe drugs | Drug: Warfarin<br> <br> Drug: Omeprazole<br> <br> Drug: Midazolam<br> <br> |
| Experimental: Treatment 2<br>single dose of digoxin | Drug: Digoxin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) of midazolam and omeprazol after each dosing |  | up to 24 hours | 
| AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) of digoxin after each dosing |  | up to 96 hours | 
| AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point) of warfarin after each dosing |  | up to 120 hours | 
| Cmax (Maximum measured concentration the analyte in plasma) of midazolam and omeprazol after each dosing |  | up to 24 hours | 
| Cmax (Maximum measured concentration the analyte in plasma) of digoxin after each dosing |  | up to 96 hours | 
| Cmax (Maximum measured concentration the analyte in plasma) of warfarin after each dosing |  | up to 120 hours |