Safety, Pharmacodynamics, and Pharmacokinetics of BIBT 1011 BS in Healthy Subjects

Study Overview
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Brief Summary
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A study to assess safety, pharmacokinetics and the effect of BIBT 986 BS, given as BIBT 1011 BS, on coagulation parameters.

Official Title
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Safety, Pharmacodynamics, and Pharmacokinetics After Single Oral Administration of 1, 5, 10, 30, 100, 200 and 400 mg BIBT 1011 BS as Drinking Solution in Healthy Subjects. An Open, Placebo-controlled, Randomised Study, Double Blind at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: Single rising doses of BIBT 1011 BS
* Drug: BIBT 1011 BS 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 ≤ 45 years Body Mass Index ≥ 18.5 and ≤ 29.9 kg/m2 Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, hormonal disorders History of orthostatic hypotension, fainting spells or blackouts Diseases of the central nervous system (such as epilepsy) or psychiatric 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 any bleeding disorder including prolonged or habitual bleeding other hematologic disease cerebral bleeding (e.g. after a car accident) commotio cerebri Intake of drugs with a long half-life (> 24 hours) within 1 month prior to administration Use of any drugs which might influence the results of the trial within 10 days prior to administration or during the 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) or inability to refrain from smoking on study days Alcohol abuse (> 60 g/day) Drug abuse Blood donation 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 clinically accepted reference range History of any familial bleeding disorder Thrombocytes < 150000/µl

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: BIBT 1011 BS<br> | Drug: Single rising doses of BIBT 1011 BS<br> <br> |
| Placebo Comparator: BIBT 1011 BS placebo<br> | Drug: BIBT 1011 BS placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of activated partial thromboplastin time (aPTT) |  | Pre-dose, up to 48 hours after start of treatment | 
| Determination of international normalized ration (INR) |  | Pre-dose, up to 48 hours after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determination of thrombin time (TT) |  | Pre-dose, up to 48 hours after start of treatment | 
| Determination of ecarin clotting time (ECT) |  | Pre-dose, up to 48 hours after start of treatment | 
| Assessment of plasma concentration time profiles of BIBT 986 BS |  | Pre-dose, up to 48 hours after start of treatment | 
| Maximum concentration of BIBT 986 BS in plasma (Cmax) |  | Pre-dose, up to 48 hours after start of treatment | 
| Area under the concentration time curve for BIBT 986 BS (AUC) |  | Pre-dose, up to 48 hours after start of treatment | 
| Time from dosing to when the plasma concentration reaches Cmax after a single extravascular dose (tmax) |  | Pre-dose, up to 48 hours after start of treatment | 
| Total mean time of residence of BIBT 986 BS- molecules in the body (MRTtot) |  | Pre-dose, up to 48 hours after start of treatment | 
| Apparent volume of distribution of the analytes during the terminal phase (Vz/f) |  | Pre-dose, up to 48 hours after start of treatment | 
| Terminal elimination half life of BIBT 986 BS in plasma (t1/2) |  | Pre-dose, up to 48 hours after start of treatment | 
| Amount excreted over the 24 hour sampling period (Ae0-24) |  | Pre-dose, up to 24 hours after start of treatment | 
| Total clearance after oral administration (CLtot/F) |  | Pre-dose, up to 48 hours after start of treatment | 
| Number of patients with adverse events |  | Up to 17 days | 
| Assessment of BIBT 986 BS plasma concentration- aPTT relationship |  | Pre-dose, up to 48 hours after start of treatment |