Single and Multiple Oral Doses of Dabigatran Etexilate in Healthy Chinese Subjects

Boehringer Ingelheim28 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Dabigatran etexilate lowDRUG

Dabigatran etexilate highDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * Age: ≥18 and ≤45 years. * Body Mass Index (BMI): ≥18 and \<25 kg/m2. * Signed and dated written informed consent prior to admission to the trial in accordance with Chinese GCP. 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 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 (NSAID), 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 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 \< 100×109 . * Pregnant female subjects.

Outcomes

Primary Outcomes

Changes in physical examination

Time frame: Day 1 and 14

Changes in vital signs

Time frame: Day 1 to 14

Changes in 12-lead electrocardiogram (ECG)

Time frame: Day 1, Day 4-10, day 14

Changes from baseline in laboratory examinations

Time frame: Day 1, 2, 4, 7, 11, 14

Occurrence of adverse events

Time frame: up to 7 days after last drug intake

Secondary Outcomes

Cmax (maximum measured concentration of the analyte in plasma)

Time frame: 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 (time from dosing to maximum measured concentration of the analyte in plasma)

Time frame: 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)

Time frame: 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)

Time frame: 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

Data from ClinicalTrials.gov

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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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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)

Time frame: 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,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)