A Study in Healthy Men to Test How Different Doses of BI 474121 Are Taken up and How They Influence the Amount of a Molecular Messenger (cGMP) in the Spinal Fluid

Study Overview
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Brief Summary
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The main objectives of this trial are: To evaluate the effect of BI 474121 on cyclic guanosine monophosphate (cGMP) levels in cerebrospinal fluid (CSF) To assess the exposure of BI 474121 in CSF relative to plasma To determine the exposure effect relationship in CSF with different oral doses of BI 474121

Official Title
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Pharmacokinetics and Pharmacodynamic Effects of Different Single Oral Doses of BI 474121 in Healthy Male Subjects

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 474121
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male 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 65 years (inclusive) BMI of 18.5 to 29.9 kg/m2 (inclusive) Signed and dated written informed consent prior to admission to the study, in accordance with Good Clinical Practice (GCP) and local legislation Exclusion Criteria: Any finding in the medical examination (including BP, PR or ECG) deviating from normal and assessed as clinically relevant by the investigator Repeated measurement of systolic blood pressure outside the range of 90 to 150 mmHg, diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the range of 45 to 90 bpm Any laboratory value outside the reference range that the investigator considers to be of clinical relevance Any evidence of a concomitant disease assessed as clinically relevant by the investigator Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders assessed as clinically relevant by the investigator 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 Further exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This trial is designed to have three parts. Part 1: single-blind, randomized, placebo-controlled. Part 2: open-label, non-randomized. Part 3: open-label, randomized.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: BI 474121<br> | Drug: BI 474121<br>* BI 474121<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum exposure-related change from baseline (calculated as ratio) of cyclic guanosine monophosphate (cGMP) in cerebrospinal fluid (CSF). | Exposure-related is the time interval around time from dosing to maximum measured concentrations (tmax) of BI 474121 in CSF. | Up to 24 hours | 
| Maximum measured concentration (Cmax) ratio of BI 474121 in cerebrospinal fluid (CSF) compared to plasma. |  | Up to Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured concentration (Cmax) of BI 474121 in plasma. |  | Up to Day 4 | 
| Maximum measured concentration (Cmax) of BI 474121 in cerebrospinal fluid (CSF). |  | Up to 24 hours | 
| Time from dosing to maximum measured concentration of BI 474121 in plasma (tmax). |  | Up to Day 4 | 
| Time from dosing to maximum measured of BI 474121 concentrations in CSF (tmax). |  | Up to 24 hours | 
| Maximum measured exposure-related cyclic guanosine monophosphate (cGMP) concentration in cerebrospinal fluid (CSF). | Exposure-related is the time interval around tmax of BI 474121 in CSF. | Up to 24 hours |