Safety, Pharmacokinetics and Pharmacodynamics After Multiple Oral Doses of BIBR 1048 MS Capsule in Healthy Japanese Male Subjects

Inclusion criteria

• Healthy male subjects according to the following criteria:

Based upon a complete medical history, including the physical examination, vital signs (blood pressure, pulse rate and body temperature), 12-lead ECG, clinical laboratory tests

• 1.1 No finding of clinical relevance
• 1.2 No evidence of a clinically relevant concomitant disease
• Age ≥20 and Age ≤35 years
• Body Mass Index (BMI) ≥18 and BMI <25 kg/m2 (Body Mass Index)
• Signed and dated written informed consent prior to admission to the trial in accordance with Japanese GCP (Ministry of Health, Labour and Welfare Ordinance No.28, March 27, 1997).

Exclusion criteria

• Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
• Subject was not able to use an adequate form of contraception from the time of the first dose on Day 1 up to end-of study examination
• Diseases of the central nervous system (such as epilepsy), psychiatric disorders or neurological disorders
• History of clinically significant orthostatic hypotension, clinically significant current or past fainting spells or blackouts.
• Chronic or relevant acute infections
• History of

• allergy/hypersensitivity (including drug allergy) which was deemed relevant to the safety assessment as judged by the investigator (excluding asymptomatic seasonal rhinitis/hay fever)
• any bleeding disorder including prolonged or habitual bleeding
• other hematologic diseases
• cerebral bleeding (e.g. after a car accident)
• concussions (head trauma resulting in injuring to brain) with or without loss of consciousness
• Intake of drugs with a long half-life (> 24 hours) within at least 1 month or less than 10 half-lives, whichever was shorter, of the respective drug prior to administration or during the trial
• Use of aspirin (including over-the-counter medications), antiplatelet agents like ticlopidine or dipyridamole, chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs, coumadin like anticoagulants, chronic use of corticosteroids, heparin or fibrinolytic agents within 14 days prior to administration up to end-of-study examination
• Participation in another trial with an investigational drug within 3 months prior to administration up to end-of-study examination
• Smoker (>10 cigarettes/day or inability to refrain from smoking during the trial)
• Alcohol abuse (more than 60 g/day; confirmed by interview)
• Drug abuse (confirmed by interview)
• Blood donation (more than 100 mL from 3 months prior to screening and any blood donation from screening up to end-of-study examination)
• Excessive physical activities (within 7 days prior to the first drug administration up to end-of-study examination)
• Any laboratory value outside the reference range that was of clinical relevance
• Known hypersensitivity to the investigational drug or its excipients
• Subject who was judged ineligible by the investigator or the sub-investigator
• History of any familial bleeding disorder
• Thrombocytes < 15 x 104 /μL