Multiple Oral Doses of BIBR 1048 MS Solution in Healthy Volunteers

Study Overview
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Brief Summary
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To assess safety, pharmacokinetics and the effect of BIBR 1048 MS on coagulation parameters.

Official Title
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Safety, Pharmacodynamics, and Pharmacokinetics After Multiple Oral Doses of 50, 100, 200, and 400 mg BIBR 1048 MS Solution Administered TID for 7 Days to Healthy Volunteer Subjects. An Open Study, Placebo-controlled Randomised Double Blind at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 1048 MS low
* Drug: BIBR 1048 MS medium 1
* Drug: BIBR 1048 MS medium 2
* Drug: BIBR 1048 MS high
* Drug: BIBR 1048 MS 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 GCP 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 History or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders History of orthostatic hypotension, fainting spells and 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 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBR 1048 MS low dose<br> | Drug: BIBR 1048 MS low<br> <br> |
| Experimental: BIBR 1048 MS medium dose 1<br> | Drug: BIBR 1048 MS medium 1<br> <br> |
| Experimental: BIBR 1048 MS medium dose 2<br> | Drug: BIBR 1048 MS medium 2<br> <br> |
| Experimental: BIBR 1048 MS high dose<br> | Drug: BIBR 1048 MS high<br> <br> |
| Placebo Comparator: BIBR 1048 Placebo<br> | Drug: BIBR 1048 MS placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in aPTT (activated partial thromboplastin time) |  | up to day 10 | 
| Change in PT (prothrombin time) |  | up to day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration) of BIBR 953 ZW |  | up to day 10 | 
| tmax (time from dosing to the maximum concentration) of BIBR 953 ZW |  | up to day 10 | 
| AUC0-∞ (area under the concentration-time curve the time interval from 0 extrapolated to infinity) of BIBR 953 ZW |  | up to day 10 | 
| Cmax,ss (maximum measured concentration at steady state) of BIBR 953 ZW |  | Day 7 | 
| Cmin,ss (minimum measured concentration at steady state) of BIBR 953 ZW |  | Day 7 | 
| Cavg (average plasma concentration at steady state) of BIBR 953 ZW |  | up to day 10 | 
| PTF (percent peak trough fluctuation for the last dosing interval) of BIBR 953 ZW |  | up to day 10 | 
| tmax,ss (time to reach Cmax) of BIBR 953 ZW |  | up to day 10 | 
| t1/2 (terminal half-life) of BIBR 953 ZW |  | up to day 10 | 
| AUCss (area under the plasma concentration-time curve of one dosing interval at steady state) of BIBR 953 ZW |  | up to day 10 | 
| MRTss (mean residence time at steady state) of BIBR 953 ZW |  | up to day 10 | 
| CLtot/F (total apparent clearance) of BIBR 953 ZW |  | up to day 10 | 
| Vz/F (apparent volume of distribution) of BIBR 953 ZW |  | up to day 10 |