Assessment of Safety, Pharmacokinetics and the Effect of BIBR 1048 MS on Coagulation Parameters in Healthy Volunteer Subjects

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 in healthy volunteer subjects.

Official Title
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Bioavailability of BIBR 953 ZW After Multiple Oral Doses of 50 and 200 mg BIBR 1048 MS Film-coated Tablet Administered BIDfor 3 Days or 200 mg BIBR 1048 MS With and Without Pre-treatment With Pantoprazole to Healthy Volunteer Subjects. Two Groups, 2-way Crossover, Randomised, Open Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 1048 MS - low dose
* Drug: BIBR 1048 MS - high dose
* Drug: BIBR 1048 MS + Pantoprazole


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 ≤ 50 years Broca ≥ - 20% and ≤ + 20% Exclusion Criteria: Any finding of the medical examination (including blood pressure, pulse rate and electrocardiogram (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 History of any bleeding disorder including prolonged or habitual bleeding History of other hematologic disease History of cerebral bleeding (e.g. after a car accident) History of commotio cerebri Intake of drugs with a long-life (> 24 hours) within 1 month prior to administration Use of any drug which might influence the results of the trial within 10 days prior to administration or during the trial Participation in another trial with investigational drug within 2 months prior to administration or during the trial Smoker (> 10 cigarettes or 3 cigars or 3 pipes/day) or inability to refrain from smoking on study days Alcohol abuse (> 60g/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 familiar bleeding disorder Thrombocytes < 150000/µl

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIBR 1048 MS<br> | Drug: BIBR 1048 MS - low dose<br> <br> Drug: BIBR 1048 MS - high dose<br> <br> |
| Experimental: BIBR 1048 MS + Pantoprazole<br> | Drug: BIBR 1048 MS - high dose<br> <br> Drug: BIBR 1048 MS + Pantoprazole<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary excretion of total BIBR 953 ZW |  | Day 1, day 2, day 3 (different time points) | 
| Peak (maximum) plasma concentration at steady state (Cmax,ss) of BIBR 953 ZW |  | Day 1, day 2, day 3 (different time points) | 
| Area under the plasma concentration-time curve at steady state (AUCss) of BIBR 953 ZW |  | Day 1, day 2, day 3 (different time points) | 
| Amount of total (free and glucuronide) BIBR 953 ZW excreted in urine over one dosing interval |  | Day 1, day 2, day 3 (different time points) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to reach the peak plasma concentration (Tmax,ss) of BIBR 953ZW |  | Day 1, day 2, day 3 (different time points) | 
| Total clearance (CLtot /f ) of BIBR 953 ZW after oral administration |  | Day 1, day 2, day 3 (different time points) | 
| Occurence of adverse events |  | 6 weeks | 
| Change from Baseline in pulse rate |  | Baseline, day 1,day 2, day 3, day 4 | 
| Change from Baseline in systolic and diastolic blood pressure |  | Baseline, day 1,day 2, day 3, day 4 | 
| Change from Baseline in clinical laboratory tests |  | Baseline, day 1,day 2, day 3, day 4 | 
| Changes from baseline in activated partial thromboplastin time (aPTT) |  | Day 1, day 2, day 3 (different time points) | 
| Changes from baseline in prothrombin time (PT) (International Normalised Ratio (INR)) |  | Day 1, day 2, day 3 (different time points) | 
| Total mean residence time (MRTtot) of BIBR 953 ZW after oral administration |  | ay 1, day 2, day 3 (different time points) |