Pharmacokinetics, Safety and Pharmacodynamics After Multiple Oral Doses of Dabigatran Etexilate Capsule in Healthy Japanese and Caucasian Male Subjects
- Registration Number
- NCT02171468
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
To investigate and compare pharmacokinetics, safety and pharmacodynamics of dabigatran etexilate following oral administration of multiple doses (110 mg and 150 mg b.i.d., 7 days) in healthy male subjects between Japanese and Caucasians
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 48
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Japanese or Caucasian 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 electrocardiogram, clinical laboratory tests
- No finding of clinical relevance
- No evidence of a clinically relevant concomitant disease
- Caucasian subjects are from a well-defined Caucasian population, both parents of Caucasians, the subjects can understand the subject information for informed consent in English and the subjects have lived 8 or less than 8 years in Japan
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Age: ≥20 and ≤45 years
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Body mass index (BMI): ≥18.5 and ≤29.9 kg/m2
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Signed and dated written informed consent before admission to the trial site
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Current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
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Subject can not use an adequate form of contraception from the time of the first dose on Day 1 up to end-of study examination
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Current diseases of the central nervous system (such as epilepsy), or psychiatric disorders or neurological disorders
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History of clinically significant orthostatic hypotension, clinically significant current or past fainting spells or blackouts
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Chronic or relevant acute infections
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History of
- allergy/hypersensitivity (including drug allergy) which is 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
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Intake of drugs with a long half-life (>24 hours) within at least 1 month or less than 10 half-lives, whichever is shorter, of the respective drug prior to administration or during the trial
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Use of aspirin (including over-the-counter medications), antipletelet agents like ticlopidine or dipyridamole, chronic administration of nonsteroidal antiinflammatory drugs , coumadin like anticoagulants, chronic use of corticosteroids, heparin or fibrinolytic agents within 28 days prior to administration up to end-of-study examination
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Participation in another trial with an investigational drug within 3 months prior to administration up to end-of-study examination
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Smoker (>10 cigarettes/day or inability to refrain from smoking during the trial)
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Alcohol abuse (more than 60 g/day; confirmed by interview)
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Drug abuse (confirmed by interview)
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Blood donation (more than 100 mL from 3 months prior to screening and any blood donation from screening up to end-of-study examination)
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Excessive physical activities (within 7 days prior to the first drug administration up to end-of-study examination)
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Any laboratory value outside the reference range that is of clinical relevance
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Known hypersensitivity to the investigational drug or its excipients
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Subject who was judged ineligible by the investigator or the sub-investigator
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History of any familial bleeding disorder
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Thrombocytes <15 x 10**4 /microL
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dabigatran high dose Dabigatran high dose - Dabigatran low dose Dabigatran low dose -
- Primary Outcome Measures
Name Time Method Occurrence of adverse events up to 10 days Cmax,ss (maximum measured concentration of the analyte in plasma at steady state) up to 7 days Changes in QT(c) intervals up to 7 days AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) up to 7 days
- Secondary Outcome Measures
Name Time Method λz,ss (terminal rate constant at steady state) up to 7 days t1/2,ss (terminal half-life at steady state) up to 7 days Cmax (maximum measured concentration) day 1 tmax (time from dosing to maximum measured concentration) day 1 AUCτ,1 (area under the concentration-time curve over a uniform dosing interval τ after administration of single dose on Day 1) day 1 tmax,ss (time from last dosing to maximum concentration at steady state) up to 7 days Cmin,ss (minimum concentration at steady state over a uniform dosing interval τ) up to 7 days MRTpo,ss (mean residence time in the body at steady state after oral administration) up to 7 days CL/F,ss (apparent clearance in the plasma at steady state after extravascular multiple dose administration) up to 7 days Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) up to 7 days RA,Cmax,13 (accumulation ratio calculated as Cmax,ss/Cmax) up to 7 days RA,AUC,13 (accumulation ratio calculated as AUCτ,ss/AUCτ,1) up to 7 days area under the curve for activated partial thromboplastin time (aPTT) 0 - 12 hours after adminstration on day 1 and day 7 area under the curve for ecarin clotting time (ECT) 0 - 12 hours after adminstration on day 1 and day 7 comparison of trough concentrations after doses 3, 5, 7, 9, 11 and 13 comparison of trough concentrations morning versus evening after doses 9, 10, 11, 12, 13