Healthy
Conditions
Brief summary
The objective of this study was to assess safety, pharmacokinetics and the effect of BIBR 953 ZW on coagulation parameters of BIBR 953 ZW after oral single doses of the prodrug, BIBR 1048 MS, in healthy male subjects. This was the first administration of this substance to humans.
Interventions
DRUGBIBR 1048 MS dose 1
DRUGBIBR 1048 MS dose 2
DRUGBIBR 1048 MS dose 3
DRUGBIBR 1048 MS dose 4
DRUGBIBR 1048 MS dose 5
DRUGPlacebo to BIBR 1048 MS
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male subjects as determined by results of screening * Signed written informed consent in accordance with Good Clinical Practice (GCP) and local legislation * Age \>= 18 and \<= 45 years * Broca \>= - 20 % and \<= + 20 %
Exclusion criteria
* Any finding 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 or 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) * commotion 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Changes from baseline in prothrombin time (PT) (International Normalised Ratio (INR)) | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after administration |
| Changes from baseline in activated partial thromboplastin time (aPTT) | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24 hours after administration |
Secondary
| Measure | Time frame |
|---|---|
| Changes from baseline in Pulse rate | up to day 3 |
| Changes from baseline in Systolic and diastolic blood pressure | up to day 3 |
| Occurrence of Adverse events | up to day 3 |
| Changes from baseline in Ecarin Clotting Time (ECT) | up to day 3 |
| Peak (maximum) plasma concentration (Cmax) of BIBR 953 ZW | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| time to reach the peak plasma concentration (tmax ) of BIBR 953 ZW | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Changes from baseline in thrombin time | up to day 3 |
| Area under the plasma concentration-time curve (AUC0-infinity) of BIBR 953 ZW from 0 to infinity | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Area under the plasma concentration-time curve of BIBR 953 ZW (AUCtf -infinity) from tf (last time point when measured plasma concentration) to infinity expressed as % of AUC0-infinity | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Terminal half-life(t1/2 ) of BIBR 953 ZW derived from non-compartmental analysis | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Total mean residence time (MRTtot ) of BIBR 953 ZW | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Total clearance (CLtot /f ) of BIBR 953 ZW after oral administration | 24 hours after administration |
| Changes from baseline in thrombin inhibition test time | up to day 3 |
| AUC0-12 h - Area under the plasma concentration-time curve of BIBR 953 ZW from 0 to 12 h | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
| Volume of distribution (Vz/f ) of BIBR 953 ZW during terminal phase after oral administration | - 0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 hours after administration |
Outcome results
None listed