Assessment of Exposure of BI 409306 in Cerebrospinal Fluid (CSF) Relative to Plasma as Well as to Evaluation of the Effect of Different Doses of BI 409306 on the cGMP (Cyclic Guanosine Monophosphate) Levels in CSF in Healthy Male Volunteers

Study Overview
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Brief Summary
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Due to the exploratory nature of this trial, there is no primary objective in a confirmatory sense. The study aims - to evaluate the effect of different doses of BI 409306 on biomarker and to assess the exposure of BI 409306

Official Title
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Randomised, Double-blind, Placebo-controlled Parallel-group Proof of Mechanism Study to Assess the Pharmacokinetics and to Evaluate the Pharmacodynamic Effect of Different Single Oral Doses of BI 409306 in Healthy Male Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 409306
* Drug: BI 409306
* Drug: BI 409306
* Drug: BI 409306 Placebo
* Drug: BI 409306


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs after 10 minutes in supine position (BP (blood pressure), PR (pulse rate), BT (body temperature)), 12-lead ECG (electrocardiogram), clinical laboratory tests Age =21 and Age =50 years BMI =18.5 and BMI =29.9 kg/m2 (Body Mass Index) Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation Exclusion criteria: Any finding of the medical examination (including BP, PR and ECG) deviating from normal and considered by the investigator as clinical relevant Abnormal values for PT (Prothrombin Time) (, aPTT (Partial Thromboplastin Time) and trombocytes considered by the investigator as clinically relevant Any evidence of a clinically relevant concomitant disease Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of the gastrointestinal tract (except appendectomy) Diseases of the central nervous system (included but not limited to any kind of seizures, stroke or psychiatric disorders) History of relevant orthostatic hypotension, fainting spells or blackouts. Chronic or relevant acute infections History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) Intake of drugs with a long half-life (> 24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Smoker, who consume more than 5 cigarettes per day Inability to refrain from smoking on trial days Alcohol abuse (more than 20 g/day): 2 units/day (14 units/week) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTcF interval >450 ms) Inability to understand and to comply with protocol requirements and restrictions and dietary regimen of trial site of additional risk factors for TdP (Torsades de points) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Male subjects who do not agree to minimize the risk of female partners becoming pregnant from the first dosing day until three month after the study completion. Acceptable methods of contraception comprises barrier contraception and a medically accepted contraceptive method for the female (intra-uterine device with spermicide, hormonal contraceptive since at least two months)

Ages Eligible for Study
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Minimum Age: 21 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 409306 low dose<br>Film-coated tablet | Drug: BI 409306<br>* Low dose film-coated tablet<br>|
| Experimental: BI 409306 low dose II<br>Film-coated tablet | Drug: BI 409306<br>* Low dose film-coated tablet<br>|
| Experimental: BI 409306 medium dose<br>Film-coated tablet | Drug: BI 409306<br>* Medium dose film-coated tablet<br>|
| Experimental: BI 409306 high dose<br>Film-coated tablet | Drug: BI 409306<br>* High dose film-coated tablet<br>|
| Experimental: Placebo<br>Film-coated tablet | Drug: BI 409306 Placebo<br>* Film-coated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum change from baseline (calculated as ratio) of biomarker |  | up to 12 weeks | 
| Cmax ratio of BI 409306 in different media |  | up to 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum measured biomarker concentration |  | up to 12 weeks | 
| Time from dosing to maximum measured in biomarker concentration |  | up to 12 weeks | 
| Cmax (maximum measured BI 409306 concentration in different media) |  | up to 12 weeks | 
| tmax (time from dosing to maximum measured BI 409306 concentration in different media) |  | up to 12 weeks |