Healthy
Conditions
Brief summary
To investigate and compare safety, pharmacokinetics and pharmacodynamics of BIBR 1048 MS following oral administration of single rising doses from 50 mg to 350 mg in healthy male subjects of Japanese and Caucasian origin. This was the first administration of this substance to subjects of Japanese origin.
Interventions
DRUGBIBR 1048 MS
DRUGPlacebo of BIBR 1048 MS
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
20 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR, Respiratory Rate and tympanic body temperature), 12- lead ECG, clinical laboratory tests * 1.1. No finding deviating from normal and of clinical relevance * 1.2. No evidence of a clinically relevant concomitant disease 2. Age ≥20 and Age ≤45 years 3. BMI ≥18 and BMI ≤25 kg/m2 (Body Mass Index) 4. Japanese subjects were from a well-defined Japanese population, both parents of Japanese origin and the subjects have Japanese passport and had lived ≤ 8 years outside Japan. 5. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice (GCP) and the local legislation.
Exclusion criteria
1. Current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 2. An unwillingness of male subjects to abstain from sexual intercourse with pregnant or lactating women, or an unwillingness if the male subject to use an adequate form of contraception as well as having their female partner(s) use another form of contraception (if the woman could become pregnant) from the time of the first dose administration until after follow up 3. Current diseases of the central nervous system (such as epilepsy), or psychiatric disorders or neurological disorders 4. History of clinically significant orthostatic hypotension, clinically significant current or past fainting spells or blackouts. 5. Chronic or relevant acute infections 6. 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) * concussions (head trauma resulting in injuring to brain) with or without loss of consciousness 7. Intake of drugs with a long half-life (\> 24 hours) within at least one month or less than 10 half-lives, whichever is shorter, of the respective drug prior to administration or during the trial 8. Use of Acetylsalicylic-Acid (ASA)-containing over-the-counter medications, clopidogrel or ticlopidine or dipyridamole, chronic administration of Non Steroidal Antiinflammatory Drugs (NSAIDs) (COX-2 inhibitors excluded), coumadin like anticoagulants, chronic use of corticosteroids, heparin and fibrinolytic agents within 14 days prior to administration or during the trial. 9. Use of all other medication including over the counter (medicinal cream, vitamin, eye drop etc.) within 7 days prior to administration or during the trial. 10. Participation in another trial with an investigational drug within three months prior to administration or during the trial 11. Smoker (\> 10 cigarettes/day or \> 3 cigars/day or \> 3 pipes/day) 12. Inability to refrain from smoking on trial days 13. Alcohol abuse (more than 21unit/week) 14. History of drug abuse 15. Blood donation (more than 100 mL within three months prior to screening administration and any blood donation from screening to follow-up) 16. Excessive physical activities (within one week prior to administration or during the trial and until follow-up) 17. Any laboratory value outside the reference range that is of clinical relevance 18. Inability to comply with dietary regimen of study centre 19. Known hypersensitivity to the drug or its excipients
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in blood pressure (BP) | At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in pulse rate (PR) | At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in respiratory rate | At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in tympanic body temperature | At screening (day -14 to -3), at day -1, pre-dose, 2, 8, 24, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in 12-Lead electrocardiogram (ECG) | At screening (day -14 to -3), at day -1, pre-dose, 2, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in haematology | At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in blood chemistry | At screening (day -14 to -3), at day -1 (pre-dose), 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Change from baseline in urinalysis | At screening (day -14 to -3), at day -1 (pre-dose), 4, 8, 12, 24, 36, 48 h after administration and on visit 5 (day 10 to day 14 after administration) |
| Occurence of adverse events | Up to visit 5 (day 10 - 14) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Aet1-t2 (amount of analyte that is eliminated in urine from the time point t1 to time point t2) | pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration | — |
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) | pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration | — |
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) | pre-dose and 0-4, 4-8, 8-12, 12-24, 24-36 and 36-48 h after administration | — |
| Cmax (maximum concentration of the analyte in plasma) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| Change from baseline for Ecarin clotting time (ECT) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | (Pharmacodynamic parameters) |
| Change from baseline for thrombin time (TT) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| Change from baseline for international normalised ratio (INR) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| Change from baseline for activated Partial Thromboplastin Time (aPTT) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| tmax (time from dosing to maximum concentration) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| AUC0-∞ (area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| AUC0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable point) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| λz (terminal rate constant in plasma) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| t1/2 (terminal half-life of the analyte in plasma) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| MRTpo (mean residence time of the analyte in the body after po administration) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| CL/F (apparent clearance of the analyte in the plasma after extravascular administration) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | — |
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) | pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36 and 48 h after administration | (Pharmacokinetic parameters) |
Outcome results
None listed