Single Rising Dose Study of BI 201335 ZW in Healthy Male Subjects

Study Overview
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Brief Summary
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The objective of the current study is to investigate safety, tolerability, and pharmacokinetics of BI 201335 ZW following administration of single rising doses from 5 mg to 1500 mg. In addition Two stage intra-subject bioavailability comparison of 600 mg BI 201335 ZW as a liquid formulation given with and without food.

Official Title
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Safety, Tolerance, and Pharmacokinetics of Single Oral Doses of 5 mg, 20 mg, 60 mg, 150 mg, 300 mg, 600 mg, 1000 mg, and 1500 mg BI 201335 ZW (PEG 400/TRIS/Water Solution) in Healthy Male Subjects, in a Randomised Double Blind, Placebo Controlled Rising Dose Study, Followed With an Open-label Intra-subject Two-stage Crossover Pilot Bioavailability Comparison of 600 mg BI 201335 ZW in a PEG 400/TRIS/Water Solution Co-administered With Food

Conditions
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Healthy

Intervention / Treatment
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* Drug: BI 201335 ZW - single rising dose
* Drug: Placebo


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 ((blood pressure (BP), pulse rate (HR)), 12-lead electrocardiogram (ECG), clinical laboratory tests Age ≥18 and Age ≤55 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 Good Clinical Practice (GCP) and the local legislation Willingness to abstain from alcohol from screening period until conclusion visit Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Any evidence of a clinically relevant concomitant disease History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders, including a clinical 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 2 months 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: 55 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 201335 ZW - single rising dose<br> | Drug: BI 201335 ZW - single rising dose<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with abnormal findings in physical examination |  | Baseline, day 3 of each treatment period, within 8 days after last administration | 
| Number of patients with clinically significant changes in vital signs |  | Baseline, day 1-3 of each treatment period, within 8 days after last administration | 
| Number of patients with clinically significant changes in 12-lead ECG (electrocardiogram) |  | Baseline, day 1, 2 in treatment period, within 8 days after last administration | 
| Number of patients with abnormal changes in laboratory parameters |  | Baseline, day 1-3 of each treatment period, within 8 days after last administration | 
| Number of patients with adverse events |  | up to 13 days | 
| Assessment of tolerability by investigator on a 4-point scale |  | on day 3 of each treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum concentration of the analyte in plasma) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| tmax (time from dosing to maximum concentration) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| AUC0-∞ (area under the concentration time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| 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) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| λz (terminal elimination rate constant in plasma) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| t1/2 (terminal half-life of the analyte in plasma) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| MRTpo (Mean residence time of the analyte in the body after oral administration) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| CL/F (apparent clearance of the analyte in the plasma after oral administration) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an oral dose) |  | pre-dose and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 12, 15, 24, 30, 36 and 48 hours post-dose |