Healthy
Conditions
Brief summary
Two substudies to assess (1) the tolerability of BIBR 953 ZW intravenous infusion at 0.1, 1 and 5 mg BIBR 953 ZW and (2) the absolute bioavailability of 100mg BIBR 1048 administered as 'acid free' tablet formulation (TF1) and (3) the bioavailability of the 100 mg tablet of BIBR 1048 relative to the tartaric acid solution of 100 mg dose strength and (4) the absolute bioavailability of the 100 mg tartaric acid solution of BIBR 1048 MS.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 50 Years
Healthy volunteers
Yes
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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| AUC0-inf (Area under the plasma concentration-time curve extrapolated to infinity) | up to 48 hours after drug administration |
| AUC0-tf (Area under the plasma concentration-time curve up to the last quantifiable plasma concentration) | up to 48 hours after drug administration |
| Cmax (Maximum plasma concentration after oral administration) | up to 48 hours after drug administration |
| Cumulative urinary excretion of BIBR 953 ZW administered intravenously | up to 48 hours after drug administration |
Secondary
| Measure | Time frame |
|---|---|
| CLtot (total clearance of drug from plasma) | up to 48 hours after infusion |
| CLren (renal clearance from plasma) | up to 48 hours after infusion |
| MRTdisp (Mean time of residence of drug molecules in the body after intravascular administration) | up to 48 hours after infusion |
| Vss (apparent volume of distribution at steady state) | up to 48 hours after infusion |
| Vz (Apparent volume of distribution during the terminal elimination phase) | up to 48 hours after infusion |
| MRTtot (total mean residence time) | up to 48 hours after oral administration |
| CLtot/F (total clearance after oral administration) | up to 48 hours after oral administration |
| changes in activated partial thromboplastin time (aPTT ) | up to 48 hours after drug administration |
| Vz/F (apparent volume of distribution of the terminal elimination phase after oral administration) | up to 48 hours after oral administration |
| changes in Ecarin clotting time (ECT) | up to 48 hours after drug administration |
| changes in thrombin time (TT) | up to 48 hours after drug administration |
| changes in vital signs (systolic and diastolic blood pressure, pulse rate) | up to 1 month |
| changes in electrocardiogram | up to 1 month |
| occurrence of adverse events | up to 1 month |
| tmax (time to reach the peak plasma concentration) | up to 48 hours after oral administration |
| changes in prothrombin time (PT) | up to 48 hours after drug administration |
| C29 (Plasma concentration of BIBR 953 ZW at 29 minutes after the start of the 30 min. infusion) | 29 minutes after start of infusion |
| t1/2 (terminal half-life) | up to 48 hours after infusion |
Outcome results
None listed