Pharmacokinetics, Safety and Pharmacodynamics After Multiple Oral Doses of Dabigatran Etexilate Capsule in Healthy Japanese and Caucasian Male Subjects

Study Overview
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Brief Summary
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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

Official Title
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Pharmacokinetics, Safety and Pharmacodynamics After Multiple Oral Doses of Dabigatran Etexilate Capsule (110 mg and 150 mg b.i.d., 7 Days) in Healthy Japanese and Caucasian Male Subjects (Open Label Study)

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran high dose
* Drug: Dabigatran low dose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Age: ≥20 and ≤45 years Body mass index (BMI): ≥18.5 and ≤29.9 kg/m2 Signed and dated written informed consent before admission to the trial site Exclusion Criteria: Current gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 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 Current diseases of the central nervous system (such as epilepsy), or 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 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 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 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 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 is 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 10**4 /microL

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dabigatran high dose<br> | Drug: Dabigatran high dose<br> <br> |
| Experimental: Dabigatran low dose<br> | Drug: Dabigatran low dose<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events |  | up to 10 days | 
| Changes in QT(c) intervals |  | up to 7 days | 
| Cmax,ss (maximum measured concentration of the analyte in plasma at steady state) |  | 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 |