Single and Multiple Oral Doses of Dabigatran Etexilate in Healthy Chinese Subjects
- Conditions
- Healthy
- Interventions
- Registration Number
- NCT02171572
- Lead Sponsor
- Boehringer Ingelheim
- Brief Summary
The objective of the current study is to investigate safety, tolerability and, pharmacokinetics of dabigatran etexilate following oral administration of single and multiple oral doses (110mg, 150 mg b.i.d., 7 days) in healthy Chinese subjects.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 28
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Healthy subjects according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (BP, PR and body temperature), 12-lead ECG, clinical laboratory tests
- No finding of clinical relevance.
- No evidence of a clinically relevant concomitant disease.
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Age: ≥18 and ≤45 years.
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Body Mass Index (BMI): ≥18 and <25 kg/m2.
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Signed and dated written informed consent prior to admission to the trial in accordance with Chinese GCP.
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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 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.
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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 was shorter, of the respective drug prior to administration or during the trial.
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Use of aspirin (including over-the-counter medications), antiplatelet agents like ticlopidine or dipyridamole, chronic administration of non-steroidal anti-inflammatory drugs (NSAID), coumadin like anticoagulants, chronic use of corticosteroids, heparin or fibrinolytic agents within 14 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 < 100×109 .
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Pregnant female subjects.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dabigatran etexilate low Dabigatran etexilate low - Dabigatran etexilate high Dabigatran etexilate high -
- Primary Outcome Measures
Name Time Method Changes in 12-lead electrocardiogram (ECG) Day 1, Day 4-10, day 14 Changes from baseline in laboratory examinations Day 1, 2, 4, 7, 11, 14 Changes in physical examination Day 1 and 14 Changes in vital signs Day 1 to 14 Occurrence of adverse events up to 7 days after last drug intake
- Secondary Outcome Measures
Name Time Method tmax (time from dosing to maximum measured concentration of the analyte in plasma) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug AUCτ,1 (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) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug Cmax (maximum measured concentration of the analyte in plasma) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug MRTpo, (mean residence time of the analyte in the body after oral administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug AUC 0-tz (area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable drug plasma concentration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug AUC0-∞ (amount of analyte that is eliminated in area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug λz (terminal rate constant in plasma) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug t1/2, (terminal half-life of the analyte in plasma) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug CL/F, (apparent clearance of the analyte in plasma following extravascular administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after single dose of study drug tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug λz,ss (terminal rate constant in plasma at steady state) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug t1/2,ss (terminal half-life of the analyte in plasma at steady state) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug CL/F,ss (apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug RA,Cmax, (calculated as Cmax,ss/Cmax) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug RA,AUC, (calculated as AUCτ,ss/AUCτ,1) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug linearity index (LI) Before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours after last multiple dose of study drug