Tolerability and Pharmacokinetics/-Dynamics of 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 an intravenous infusion of 0.5 and 1.0 mg (actual 0.8 mg) BIBT 986 BS per hour over 32 hours as well as pharmacokinetics and the effect on blood coagulation parameters

Official Title
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Tolerability and Pharmacokinetics/-Dynamics of 0.5 mg and 1.0 mg (Actual 0.8 mg) of BIBT 986 BS Per Hour Given as IV Infusion Over 32 Hours 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 - low
* Drug: BIBT 986 BS - high
* 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 Abnormal PT, TT, aPTT (must be within the normal range after no more than one repeated test), thrombocytes < 150000/μl (two repeats of the first test) Evidence of hematuria either macroscopically detectable or microscopic on urinalysis (normal microscopic results after no more than one repeated test) Evidence of blood dyscrasia, hemorrhagic diathesis, severe thrombocytopenia, cerebrovascular hemorrhage, bleeding tendencies associated with active ulceration or overt bleeding of gastrointestinal, respiratory or genitourinary tract or any disease or condition with hemorrhagic tendencies (e.g. cerebral aneurysm, dissecting aorta, Central nervous system (CNS) trauma, retinopathy, nephrolithiasis) Recent or contemplated diagnostic or therapeutic procedures with potential for uncontrollable bleeding (e.g. spinal puncture, lumbar block anaesthesia, surgery of CNS or eye or surgery resulting in large open surfaces) within 14 days before or after drug administration of this clinical trial Occult blood in 1 of 3 subsequent faecal samples collected for the pre-study examination 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, within 14 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 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 Veins unsuited for i.v. puncture and administration of prolonged infusions on either arm (e.g. veins which are difficult to locate, access or puncture, veins with a tendency to rupture during or after puncture, etc.)

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 - low<br> | Drug: BIBT 986 BS - low<br> <br> |
| Experimental: BIBT 986 BS - high<br> | Drug: BIBT 986 BS - high<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 |
| --- | --- | --- |
| Cmax (maximum measured concentration of the analyte in plasma) |  | up to 48 hours post dose | 
| CT (concentration of the analyte at the end of drug infusion) |  | up to 48 hours post dose | 
| Css (steady state concentration of the analyte in plasma following a constant rate infusion) |  | up to 48 hours post dose | 
| Tmax (time from dosing to the maximum concentration of the analyte in plasma) |  | up to 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 after single dose administration) |  | up to 48 hours post dose | 
| t1/2 (Terminal half-life of the analyte in plasma after single dose administration) |  | up to 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 drug plasma concentration after single dose administration) |  | up to 48 hours post dose | 
| λz (terminal rate constant of the analyte in plasma) |  | up to 48 hours post dose | 
| MRTinf (mean residence time of the analyte in the body after intravenous infusion) |  | up to 48 hours post dose | 
| CL (Total clearance of the analyte in plasma following intravascular administration) |  | up to 48 hours post dose | 
| Vss (Apparent volume of distribution at steady state following intravascular administration) |  | up to 48 hours post dose | 
| Vz (apparent volume of distribution during the terminal phase λz following intravascular administration) |  | up to 48 hours post dose | 
| Amount of parent drug eliminated in urine (Ae) |  | up to 48 hours post dose | 
| Change in activated partial thromboplastin time (aPTT) |  | up to 48 hours post dose | 
| Change in prothrombin time (PT) |  | up to 48 hours post dose | 
| Change in ecarin clotting time (ECT) |  | up to 48 hours post dose | 
| Change in thrombin time (TT) |  | up to 48 hours post dose | 
| Number of subjects with adverse events |  | up to 4 days | 
| Number of subjects with clinically significant changes in vital signs | Pulse rate, systolic & diastolic blood pressure | up to 4 days | 
| Change in International Normalised Ratio (INR) |  | up to 48 hours post dose | 
| Fraction of administered drug excreted unchanged in urine (fe) |  | up to 48 hours post dose | 
| CLR (renal clearance of the analyte in plasma following intravascular administration) |  | up to 48 hours post dose |