Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Doses Oral BIRB 796 BS in Healthy Human Subjects

Study Overview
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Brief Summary
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To assess safety, pharmacokinetics and pharmacodynamics of BIRB 796 BS in escalating single doses, with and without a 64 g fat breakfast at one selected dose.

Official Title
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Safety, Pharmacokinetics and Pharmacodynamics of Single Rising Doses (1, 4, 15, 50, 100, 200, 400, and 600 mg) Oral BIRB 796 BS in Healthy Human Subjects. A Placebo Controlled, Randomised Study, Double Blinded at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 796 BS
* Drug: Placebo
* Other: high fat 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 <= 45 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 Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant ot the trial as judged by the investigator Intake of drugs with a long half-life (> 24 hours) (= 1 month prior to administration or during the trial) Use of any drugs, which might influence the results of the trial (= 10 days prior to administration or during the trial) Participation in another trial with an investigational drug (=2 months prior to administration or during trial) Smoker (> 10 cigarettes of > 3 cigars of > 3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation > 400 ml (=1 month prior to administration of during the trial) Excessive physical activities (= 5 days prior to administration or during the trial) Any laboratory value outside the reference range of clinical relevance (but not exclusive to) total white cell count >= 10 x 10**9/L, C-reactive protein >= 4.5 mg/L, any haemoglobin or > 15 mg/dl protein on urine dipstick History of any familial bleeding disorder

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 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 |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |
| Experimental: BIBR 796 BS food effect<br> | Drug: BIBR 796 BS<br> <br> Other: high fat standardized breakfast<br> <br> |
| Experimental: BIBR 796 BS<br> | Drug: BIBR 796 BS<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with clinically relevant changes in vital signs |  | Baseline, up to 96 hours after drug administration | 
| Number of subjects with clinically relevant changes in laboratory measurements |  | Baseline, up to 96 hours after drug administration | 
| Number of subjects with clinically relevant changes in electrocardiograms (ECG) |  | Baseline, up to 96 hours after drug administration | 
| Number of subjects with adverse events |  | up to 96 hours after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of the analyte in plasma (Cmax) |  | up to 48 hours after drug administration | 
| Area under the concentration-time curve of the analyte in plasma from time zero to infinity (AUC0-inf) |  | up to 48 hours after drug administration | 
| Time from dosing to the maximum concentration of the analyte in plasma (Tmax) |  | up to 48 hours after drug administration | 
| Terminal rate constant of the analyte in plasma (λz) |  | up to 48 hours after drug administration | 
| Half life of the analyte in plasma (t1/2) |  | up to 48 hours after drug administration | 
| Mean residence time of the analyte in the body (MRTtot) |  | up to 48 hours after drug administration | 
| Apparent clearance of the analyte in plasma (CL/F) |  | up to 96 hours after drug administration | 
| Apparent volume of distribution during the terminal phase λz (Vz/F) |  | up to 48 hours after drug administration | 
| Mac-1/L selectin ratio of formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated to unstimulated neutrophils |  | up to 48 hours after drug administration | 
| Mac-1/L selectin ratio of TNFalpha-stimulated to unstimulated neutrophils |  | up to 48 hours after drug administration | 
| Percent changes in TNFalpha production | after ex vivo stimulation of whole blood with endotoxin | up to 48 hours after drug administration |