Safety, Tolerance, and Pharmacokinetics of BILN 2061 ZW in Healthy Male Subjects, Combined With Preliminary Evaluation of Food Effect

Study Overview
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Brief Summary
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To assess the safety, tolerance and pharmacokinetics of 5 mg to 2400 mg BILN 2061 ZW In rising single doses With and without a 64 g fat breakfast at one selected dose

Official Title
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Safety, Tolerance, and Pharmacokinetics of Single Oral Doses of 5 mg, 20 mg, 60 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg, 1000 mg, 1200 mg, 1500 mg, 2000 mg and 2400 mg BILN 2061 ZW (PEG 400: Ethanol Solution) in Healthy Male Subjects, Combined With Preliminary Evaluation of Food Effect of the Dose of 200 mg (Two-Stage Trial Design With Randomised Double Blind Placebo Controlled Rising Dose Part and Subsequent Open Intraindividual Comparison Part)

Conditions
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Healthy

Intervention / Treatment
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* Drug: BILN 2061 ZW single rising doses
* Drug: Placebo
* Drug: BILN 2061 ZW fixed dose
* Other: Standardized breakfast


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subjects as determined by results of screening Signed written informed consent in accordance with good clinical practice (GCP) and local legislation Age ≥ 18 and ≤ 50 years Broca ≥ - 20 % and ≤ + 20 % Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders, including a history of viral hepatitis, or serological evidence of active Hepatitis B or Hepatitis C infection History of orthostatic hypotension, fainting spells and blackouts Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration Use of any drugs which might 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 1 month prior to administration or during the trial Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation within 1 month prior to administration or during the trial Excessive physical activities within 5 days prior to administration or during the trial Any laboratory value outside the clinically accepted reference range and of clinical relevance History of any familial bleeding disorder

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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BILN 2061 ZW single rising doses<br> | Drug: BILN 2061 ZW single rising doses<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: BILN 2061 ZW fixed dose fed<br> | Drug: BILN 2061 ZW fixed dose<br> <br> Other: Standardized breakfast<br> <br> |
| Active Comparator: BILN 2061 ZW fixed dose fasted<br> | Drug: BILN 2061 ZW fixed dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with clinically relevant changes in vital signs (systolic and diastolic blood pressure, pulse rate) |  | Pre-dose, up to 48 hours after drug administration | 
| Changes from baseline in laboratory tests |  | Pre-dose and 48 hours after drug administration | 
| Number of patients with clinically relevant changes in 12-lead ECG |  | Pre-dose, up to 48 hours after drug administration | 
| Changes from baseline in physical examination |  | Pre-dose and 48 hours after drug administration | 
| Number of patients with adverse events |  | Up to 48 hours after drug administration | 
| Global assessment of tolerability by the investigator on a 4-point scale |  | Up to 48 hours after drug administration | 
| Maximum concentration of the analyte in plasma after a single dose administration (Cmax) |  | up to 48 hours after drug administration | 
| Area under the concentration-time curve of the analyte in plasma from time 0 to infinity (AUC0-infinity) |  | up to 48 hours after drug administration | 
| Time to reach Cmax following a single dose administration (tmax) |  | up to 48 hours after drug administration | 
| Elimination half-life of the analyte in plasma (t1/2) |  | up to 48 hours after drug administration | 
| Total oral clearance of the analyte from plasma after oral administration, divided by F (bioavailability factor) (CL/F) |  | up to 48 hours after drug administration | 
| Total mean residence time of the analyte in plasma (MRT) |  | up to 48 hours after drug administration | 
| Apparent volume of distribution during the terminal elimination phase (Vz/F) |  | up to 48 hours after drug administration | 
| Amount of intact drug excreted in urine (Au) |  | up to 48 hours after drug administration |