Bioavailability of BIBR 953 ZW After Administration of BIBR 1048 MS in Healthy Subjects

Study Overview
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Brief Summary
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Study to assess the amount of BIBR 953 ZW in urine and concentrations in plasma after administration of 50 mg of BIBR 1048 bid over three days each administered as two experimental formulations relative to drinking solution with and without coadministration of 40 mg Pantoprazole.

Official Title
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Bioavailability of BIBR 953 ZW After 50 mg of BIBR 1048 MS (Oral Prodrug of BIBR 953) in 2 Experimental Formulations Relative to Drinking Solution of BIBR 1048 MS, Each Treatment Given Bid Over 3 Days in Healthy Subjects. Intraindividual Comparison (3-way Crossover) With and Without Pantoprazole, Randomised, Open.

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 1048 MS Capsule I
* Drug: BIBR 1048 MS Capsule K
* Drug: Pantoprazole
* Drug: BIBR 1048 MS drinking solution


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 ≤ 55 years BMI ≥ 18.5 and ≤ 29.9 kg/m2 Exclusion Criteria: Any finding at the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance History of or current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic, hormonal disorders History of relevant 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 that 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: 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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Period 1: BIBR 1048 MS with Pantoprazole<br>Three treatments of different formulations of 50 mg BIBR 1048 MS (bid for 3 days) with 40 mg Pantoprazole (bid). Randomised sequence. BIBR 1048 MS Capsule I with pantoprazole (bid for 3 days); BIBR 1048 MS Capsule K with pantoprazole (bid for 3 days); BIBR 1048 MS Drinking solution with Pantoprazole (bid for 3 days) | Drug: BIBR 1048 MS Capsule I<br>* 25 mg BIBR 1048 MS<br>Drug: BIBR 1048 MS Capsule K<br>* 50 mg BIBR 1048 MS<br>Drug: Pantoprazole<br>* 40 mg pantoprazole<br>Drug: BIBR 1048 MS drinking solution<br>* 50 mg BIBR 1048 MS powder plus solution<br>|
| Experimental: Period 2: BIBR 1048 MS<br>Three treatments of different formulations of 50 mg BIBR 1048 MS (bid for 3 days) without Pantoprazole. Fixed sequence. BIBR 1048 MS Capsule K (bid for 3 days); BIBR 1048 MS Drinking solution (bid for 3 days) | Drug: BIBR 1048 MS Capsule K<br>* 50 mg BIBR 1048 MS<br>Drug: BIBR 1048 MS drinking solution<br>* 50 mg BIBR 1048 MS powder plus solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total amount of BIBR 953 ZW excreted into urine during one dosing interval (Ae0-12) |  | Day 1 to day 10 | 
| AUCss (Area under the plasma concentration-time curve at steady state) of BIBR 953 ZW |  | 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours after administration of study drug on day 3 of second treatment period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax,ss (maximum concentration at steady state) of BIBR 953 ZW |  | 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours after administration of study drug on day 3 of second treatment period | 
| tmax,ss (time from dosing to Cmax at steady state) of BIBR 953 ZW |  | 0.5, 1, 1.5, 2, 4, 6, 8, 12 hours after administration of study drug on day 3 of second treatment period |