Tolerability and Pharmacokinetics/-Dynamics of Single Rising Doses BIBT 986 BS in Healthy Male Subjects

Study Overview
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Brief Summary
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Study to assess the tolerability of BIBT 986 BS after intravenous infusions of 0.1, 0.3, 1.0, 2.5, 5.0, and 10 mg, to assess the pharmacokinetics of BIBT 986 BS after intravenous infusion and to assess the effect of BIBT 986 BS on blood coagulation parameters

Official Title
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Tolerability and Pharmacokinetics/-Dynamics of Single Rising Doses of 0.1 mg, 0.3 mg, 1.0 mg, 2.5 mg, 5.0 mg, and 10.0 mg BIBT 986 BS (IV Infusion Over 30 Minutes) in Healthy Male Subjects. Placebo Controlled, Double Blind Randomised at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBT 986 BS - single rising dose
* 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 <= 55 years BMI >= 18.5 and <= 29.9 kg/m2 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 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 Any bleeding disorder including prolonged or habitual bleeding History of other hematologic disease, cerebral bleeding (e.g. after a car accident), commotio cerebri Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Seasonal rhinitis Thrombocytes < 150000/μl 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 or >3 cigars or >3 pipes/day) Alcohol abuse (> 60 g/day) Drug abuse Use of methylxanthine-containing drinks or foods (coffee, tea, cola, energy drinks, chocolate, etc.), grapefruit or grapefruit juice, alcohol, green tea, or tobacco < 5 days prior to administration of study drug or during trial Blood donation or loss > 400 ml, < 1 month prior to administration or during the trial Excessive physical activities < 5 days prior to administration of study drug or during trial Clinically relevant laboratory abnormalities Any ECG value outside of the reference range of clinical relevance including, but not limited to QRS interval > 110 ms or QTcB > 450 ms 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: 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: BIBT 986 BS - single rising dose<br> | Drug: BIBT 986 BS - 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 |
| --- | --- | --- |
| AUC0-∞ (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity after single dose administration) |  | up to 48 hours after start of infusion | 
| AUC0-tz (Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration after single dose administration) |  | up to 48 hours after start of infusion | 
| C29 (plasma concentration of BIBT 986 BS at the end of infusion) |  | 29 minutes after start of infusion | 
| t1/2 (Terminal half-life of the analyte in plasma after single dose administration) |  | up to 48 hours after start of infusion | 
| CL (Total clearance of the analyte in plasma following intravascular administration) |  | up to 48 hours after start of infusion | 
| Vss (Apparent volume of distribution at steady state following intravascular administration) |  | up to 48 hours after start of infusion | 
| urinary excretion of BIBT 986 BS |  | up to 48 hours after start of infusion | 
| CLR (Renal clearance of the analyte in plasma following intravascular administration) |  | up to 48 hours after start of infusion | 
| MRT (Mean residence time of drug molecules in the body after intravascular administration) |  | up to 48 hours after start of infusion | 
| Change in activated partial thromboplastin time (aPTT) |  | up to 48 hours after start of infusion | 
| Change in International Normalised Ratio (INR) |  | up to 48 hours after start of infusion | 
| Change in ecarin clotting time (ECT) |  | up to 48 hours after start of infusion | 
| Change in thrombin time (TT) |  | up to 48 hours after start of infusion | 
| Number of patients with clinically significant findings in vital signs | pulse rate, blood pressure | up to 48 hours after start of infusion | 
| Number of patients with clinically significant findings in electrocardiogram |  | up to 48 hours after start of infusion | 
| Number of patients with clinically significant findings in laboratory tests |  | up to 48 hours after start of infusion | 
| Number of patients with adverse events |  | up to 48 hours after start of infusion | 
| Number of patients with histamine in blood |  | up to 48 hours after start of infusion |