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

Boehringer Ingelheim7 enrolled

Overview

To investigate safety, pharmacokinetics and pharmacodynamics of BIBR 1048 MS following oral administration of multiple doses (150 mg b.i.d., 7 days)

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

BIBR 1048 MSDRUG

150 mg capsules, b.i.d, 7 days

Eligibility

Sex: MALEMin age: 20 YearsMax age: 35 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. Age ≥20 and Age ≤35 years 3. Body Mass Index (BMI) ≥18 and BMI \<25 kg/m2 (Body Mass Index) 4. 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: 1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 2. 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 3. Diseases of the central nervous system (such as epilepsy), 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 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 7. 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 8. 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 9. Participation in another trial with an investigational drug within 3 months prior to administration up to end-of-study examination 10. Smoker (\>10 cigarettes/day or inability to refrain from smoking during the trial) 11. Alcohol abuse (more than 60 g/day; confirmed by interview) 12. Drug abuse (confirmed by interview) 13. Blood donation (more than 100 mL from 3 months prior to screening and any blood donation from screening up to end-of-study examination) 14. Excessive physical activities (within 7 days prior to the first drug administration up to end-of-study examination) 15. Any laboratory value outside the reference range that was of clinical relevance 16. Known hypersensitivity to the investigational drug or its excipients 17. Subject who was judged ineligible by the investigator or the sub-investigator 18. History of any familial bleeding disorder 19. Thrombocytes \< 15 x 104 /μL

Outcomes

Primary Outcomes

Change from baseline in physical examination

Time frame: within 14 days prior to drug administration until up to 18 days post drug administration

Change from baseline in vital signs

Time frame: within 14 days prior to drug administration until up to 18 days post drug administration

Change from baseline in 12-lead electrocardiogram (ECG)

Time frame: within 14 days prior to drug administration until up to 18 days post drug administration

Change from baseline in clinical laboratory tests

Time frame: within 14 days prior to drug administration until up to 18 days post drug administration

Number of participants with adverse events

Time frame: within 14 days prior to drug administration until up to 18 days post drug administration

Secondary Outcomes

Changes in activated partial thromboplastin time (aPTT)

Time frame: Day 1 and 7 prior, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 h after drug administration (morning), Day 2 to 6 prior drug administration (morning), Day 5 and 6 prior drug administration (evening), Day 7 24, 36, 48 h after final drug administration

Changes in ecarin clotting time (ECT)

Changes in thrombin time (TT)

Data from ClinicalTrials.gov

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Changes in prothrombin time expressed as international normalised ratio (INR)

Maximum measured concentration of the analyte in plasma (Cmax)

Time from dosing to maximum measured concentration of the analyte in plasma (tmax)

Area under the concentration-time curve of the analyte in plasma over a uniform dosing interval τ after administration of the single dose on Day 1 (AUCτ,1)

Time frame: Day 1 before, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after drug administration in the morning

Amount of analyte that is eliminated in urine from the time point t1 to time point t2 ( Aet1-t2 )

Time frame: Day 1: 0-4, 4-8, 8-12 and 12-24 hours after the first drug administration, on Day 7: 0-4, 4-8, 8-12, 12-24, 24-48 and 48-72 hours after the last drug administration

Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2 )

Time frame: Day 1: 0-4, 4-8, 8-12 and 12-24 hours after the first drug administration, on Day 7: 0-4, 4-8, 8-12, 12-24, 24-48 and 48-72 hours after the last drug administration

Fraction of analyte eliminated in urine from time point t1 to time point t2 (fet1-t2)

Time frame: Day 1: 0-4, 4-8, 8-12 and 12-24 hours after the first drug administration, on Day 7: 0-4, 4-8, 8-12, 12-24, 24-48 and 48-72 hours after the last drug administration

Maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmax,ss)