Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BIRB 1017 BS as a Solution in PEG 400 / 26% Ethanol Administered to Healthy Male Subjects

Study Overview
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Brief Summary
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Study to assess safety, tolerability and pharmacokinetics of BIRB 1017 BS in single rising oral doses of 5 to 800 mg in a polyethylene glycol 400 (PEG 400) / 26% ethanol solution in healthy male subjects

Official Title
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Safety, Tolerability, and Pharmacokinetics of Single Rising Oral Doses of BIRB 1017 BS (5, 25, 100, 250, 500, and 800 mg) as a Solution in PEG 400 / 26% Ethanol Administered to Healthy Male Subjects. Placebo Controlled and Blinded at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 1017 BS powder
* Drug: Placebo


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 BMI >18.5 and <29.9 kg/m2 (Body Mass Index) Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate, and electrocardiogram) deviating from normal and of clinical relevance Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, haematological, oncological or hormonal disorders Surgery of gastrointestinal tract (except appendectomy) Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders Relevant history of orthostatic hypotension, fainting spells or blackouts 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) (< 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 study drug administration or expected during the trial) Participation in another trial with an investigational drug (< 2 months prior to administration or expected during trial) Smoker (> 10 cigarettes or >3 cigars or >3 pipes/day) Inability to refrain from smoking on trial days Alcohol abuse (> 60 g/day) Drug abuse Blood donation or loss > 400 mL, < 1 month prior to administration or expected during the trial Excessive physical activities (within 5 days prior to administration or during the trial) Clinically relevant laboratory abnormalities Any electrocardiogram value outside of the reference range and of clinical relevance including, but not limited to QRS interval > 110 ms or QTcB > 450 ms or QT >500 ms Known hypersensitivity to the drug or its excipients Inability to comply with dietary regimen of study centre Inability to comply with investigator's instructions

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: BIRB 1017 BS in single rising doses<br> | Drug: BIBR 1017 BS powder<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* PEG 400<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of safety and tolerability by the investigator on a 4-point scale |  | at day 5-10 | 
| Number of patients with adverse events |  | up to 25 days | 
| Number of patients with clinically significant changes in vital signs (pulse rate, systolic and diastolic blood pressure) |  | up to day 10 | 
| Number of patients with abnormal changes in clinical laboratory tests |  | up to day 10 | 
| Number of patients with clinically relevant effect on electrocardiogram parameters |  | up to day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of BIRB 1017 BS in plasma (Cmax) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Time from dosing to maximum concentration (tmax) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Area under the concentration-time curve of the analyte in plasma ofer the time interval from 0 to the last quantifiable analyte plasma concentration (AUC0-infinity) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable analyte plasma concentration (AUC0-tz) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Terminal elimination rate constant in plasma (λz) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Terminal half-life of the analyte in plasma (t1/2) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Mean residence time of the analyte in the body (MRT) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Apparent oral clearance of the analyte in the plasma after oral administration (CL/F) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug | 
| Apparent volume of distribution during the terminal phase λz following an oral dose (Vz/F) |  | pre-dose and 0:30, 1:00, 1:30, 2:00, 2:30, 3:00, 4:00, 5:00, 6:00, 8:00, 12:00, 15:00, 24:00, 34:00, and 48:00 hours after administration of study drug |