Safety, Pharmacokinetics and Pharmacodynamics of BIRB 796 BS Tablets Administered to Healthy Human Subjects

Study Overview
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Brief Summary
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Study to assess safety, pharmacokinetics and pharmacodynamics of BIRB 796 BS in escalating multiple doses with and without a 64 g fat breakfast at the 50 mg dose level

Official Title
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Safety, Pharmacokinetics and Pharmacodynamics of BIRB 796 BS Tablets (20, 30, 150, 300, and 600 mg) Administered Orally to Healthy Human Subjects Once Daily for 7 Days. A Placebo Controlled, Randomised, Double Blinded Study

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 796 BS
* Drug: Placebo
* Other: high fat 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 and local legislation Age ≥ 18 and ≤ 45 years Broca ≥ - 20% and ≤ + 20% Exclusion Criteria: Any findings of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders Surgery of gastrointestinal tract (except appendectomy) 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 or during the trial) Use of any drugs which might influence the results of the trial within 10 days prior to administration or during trial Participation in another trial with an investigational drug within 2 months prior to administration or during trial Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) Inability to refrain from smoking on study days Alcohol abuse (> 60 g/day) Drug abuse Blood donation > 400 ml 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 reference range of clinical relevance including, but not limited to total white cell count ≥ 10 x 10**9/L, C-reactive protein ≥ 4.5 mg/L, Gamma-Glutamyl Transferase ≥ 40 U/L, any hemoglobin or > 15 mg/dl protein or urine dipstick, abnormal Multitest® assessment of cellular immunity History of any familial bleeding disorder Inability to comply with dietary regimen of study centre

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 |
| --- | --- |
| Experimental: BIBR 796 BS, fasted<br>dose escalation | Drug: BIBR 796 BS<br> <br> |
| Experimental: BIBR 796 BS, fed<br>50 mg BIRB 796 BS (food effect) | Drug: BIBR 796 BS<br> <br> Other: high fat breakfast<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 clinically relevant changes in laboratory parameters |  | up to day 16 | 
| Number of patients with abnormal findings in electrocardiogram (ECG) |  | up to day 16 | 
| Number of patients with adverse events |  | up to 30 days | 
| Assessment of tolerability on a 4-point scale |  | day 16 | 
| Number of patients with clinically relevant changes in vital signs |  | up to 16 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) for several time points |  | up to day 9 | 
| Area under the plasma concentration-time curve (AUC) for several time points |  | up to day 9 | 
| Time to maximum concentration (tmax) |  | up to day 9 | 
| Elimination rate constant (λz) |  | up to day 9 | 
| Terminal half-life (t1/2) |  | up to day 9 | 
| Mean residence time (MRT) |  | up to day 9 | 
| Apparent clearance (CL/f) |  | up to day 9 | 
| Apparent volume of distribution (Vz/F) |  | up to day 9 | 
| Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with formyl-methionyl-leucyl-phenylalanine (fMLP) | Change in the Mac-1 / L-selectin ratio | up to day 9 | 
| Assessment of neutrophil and monocyte activation by ex vivo stimulation of whole blood with tumour necrosis factor (TNF) α | Change in the Mac-1 / L-selectin ratio | up to day 9 | 
| Assessment of TNFα production by ex vivo stimulation of whole blood with endotoxin |  | up to day 9 | 
| Changes in cellular immune response measured by Multitest® |  | Day 8 |