Bioavailability of BIBR 953 ZW After BIBR 1048 (Oral Pro-drug of BIBR 953 ZW) Administered as Hydroxypropyl Methylcellulose (HPMC) Polymorph II Capsule Relative to HPMC Polymorph I Capsule in Healthy Subjects.

Study Overview
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Brief Summary
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Investigation of the relative bioavailability of BIBR 953 ZW after administration of 150 mg BIBR 1048 polymorph II versus BIBR 953 ZW after administration of 150 mg BIBR 1048 polymorph I in HPMC capsules

Official Title
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Bioavailability of BIBR 953 ZW After 150 mg of BIBR 1048 (Oral Pro-drug of BIBR 953 ZW) Administered as HPMC Polymorph II Capsule Relative to 150 mg HPMC Polymorph I Capsule in Healthy Subjects. A Two-way Crossover, Randomised, Open Trial

Conditions
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Healthy

Intervention / Treatment
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* Drug: BIBR 1048 MS polymorph II
* Drug: BIBR 1048 MS polymorph I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy female and 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 of more than 400 ml within 4 weeks 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 reference range of clinical relevance History of any familial bleeding disorder Platelets < 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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All

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 polymorph II<br> | Drug: BIBR 1048 MS polymorph II<br> <br> |
| Active Comparator: BIBR 1048 MS polymorph I<br> | Drug: BIBR 1048 MS polymorph I<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC0-infinity (area under the plasma concentration-time curve of BIBR 953 ZW from 0 to infinity) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| AUC0-tz |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| Cmax (maximum measured plasma concentration of BIBR 953 ZW) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| tmax (time from dosing to when the plasma concentration reaches Cmax after extravascular doses ) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| t1/2 (half life) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| MRTpo (mean time of residence of drug molecules in the body) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| CL/F (apparent clearance after oral administration) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| Vz/F (apparent volume of distribution) |  | 0 h (predose), 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, 12 h, 24 h, 48 h, and 72 h after drug administration | 
| Changes in ECG |  | up to 31 days | 
| Changes in systolic and diastolic blood pressure |  | up to 31 days | 
| Occurrence of adverse events |  | up to 31 days | 
| Assessment of tolerability by investigator on a four-point scale |  | up to 31 days |