Safety and Pharmacokinetics of Single Rising Oral Doses of BI 224436 ZW in Healthy Male Volunteers.

Study Overview
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Brief Summary
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To investigate safety and pharmacokinetics of BI 224436 ZW

Official Title
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Safety and Pharmacokinetics of Single Rising Oral Doses of BI 224436 ZW at 6.2 mg, 12.5 mg, 25 mg, 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 900 mg and 1200 mg Dose Levels in Healthy Male Volunteers (Randomized, Double-blind, Placebo-controlled Within Dose Groups)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 224436
* Drug: Placebo to BI 224436


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males Age ≥21 and Age ≤50 years Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with Good clinical practice (GCP) and the local legislation. Exclusion Criteria: Any finding of the medical examination (including blood pressure (BP), pulse rate (PR) and electrocardiogram (ECG)) deviating from normal and of clinical relevance 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 (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts HIV infection and other 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 or during the trial Use of drugs which might reasonably influence the results of the trial within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within one month prior to administration or during the trial Smoker (>10 cigarettes or >3 cigars or >3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (more than 60 g/day) 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 treatment period) Any laboratory value outside the reference range that is of clinical relevance A baseline prolongation of QT/QTc interval (e.g., a QTc interval ≥450 ms) A history of additional risk factors for Torsades de points (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome) Bradycardia (PR <60 beats/min)

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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BI 224436<br> | Drug: BI 224436<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo to BI 224436<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum measured concentration of the analyte in plasma |  | up to 72 hours | 
| area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to 24 |  | up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity |  | up to 72 hours | 
| minimum observed concentration at 24 hours |  | up to 24 hours | 
| terminal half-life of the analyte in plasma |  | up to 72 hours | 
| time from dosing to maximum measured concentration of the analyte in plasma |  | up to 72 hours | 
| apparent clearance of the analyte in plasma |  | up to 72 hours | 
| apparent volume of distribution during the terminal phase λz |  | up to 72 hours | 
| apparent volume of distribution |  | up to 72 hours | 
| mean residence time of the analyte in the body after single oral administration |  | up to 72 hours | 
| terminal rate constant in plasma |  | up to 72 hours | 
| the last measurable concentration in the concentration-time profile |  | up to 72 hours | 
| the extrapolated Area under the curve from the time of the last measurable concentration in the concentration-time profile to infinity |  | up to 72 hours | 
| the percentage of the Area under the concentration-time curve until infinity, that is determined by extrapolation |  | up to 72 hours | 
| amount of analyte that is eliminated in urine from the time point t0 to time point t4 |  | up to 4 hours | 
| amount of analyte that is eliminated in urine from the time point t4 to time point t8 |  | from 4 to 8 hours | 
| amount of analyte that is eliminated in urine from the time point t8 to time point t12 |  | from 8 to 12 hours | 
| amount of analyte that is eliminated in urine from the time point t12 to time point t24 |  | from 12 to 24 hours | 
| fraction of analyte eliminated in urine from time point t0 to time point t24 |  | up to 24 hours | 
| renal clearance of the analyte from the time point t0 until the time point t24 |  | up to 24 hours |