Clinical trial NCT02171572: Single and Multiple Oral Doses of Dabigatran Etexilate in Healthy Chinese Subjects
Official title: Safety, Tolerability and Pharmacokinetics Study After Single and Multiple Oral Doses of Dabigatran Etexilate Capsule (110mg,150 mg b.i.d., 7 Days) in Healthy Chinese Subjects (Open Label Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-24
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Changes in physical examination
timeFrame: Day 1 and 14
measure: Changes in vital signs
timeFrame: Day 1 to 14
measure: Changes in 12-lead electrocardiogram (ECG)
timeFrame: Day 1, Day 4-10, day 14
measure: Changes from baseline in laboratory examinations
timeFrame: Day 1, 2, 4, 7, 11, 14
measure: Occurrence of adverse events
timeFrame: up to 7 days after last drug intake
Secondary outcomes:
measure: Cmax (maximum measured concentration of the analyte in plasma)
timeFrame: 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
measure: tmax (time from dosing to maximum measured concentration of the analyte in plasma)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: %AUCtz-∞ (the percentage of the AUC0-∞ that is obtained by extrapolation)
timeFrame: 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
measure: λz (terminal rate constant in plasma)
timeFrame: 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
measure: t1/2, (terminal half-life of the analyte in plasma)
timeFrame: 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
measure: MRTpo, (mean residence time of the analyte in the body after oral administration)
timeFrame: 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
measure: CL/F, (apparent clearance of the analyte in plasma following extravascular administration)
timeFrame: 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
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular administration)
timeFrame: 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
measure: Cmax,ss (maximum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: 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
measure: tmax,ss (time from last dosing to maximum concentration of the analyte in plasma at steady state)
timeFrame: 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
measure: Cmin,ss (minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: 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
measure: AUCτ,ss (area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ)
timeFrame: 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
measure: λz,ss (terminal rate constant in plasma at steady state)
timeFrame: 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
measure: t1/2,ss (terminal half-life of the analyte in plasma at steady state)
timeFrame: 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
measure: MRTpo,ss (mean residence time of the analyte in the body at steady state after oral administration)
timeFrame: 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
measure: CL/F,ss (apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration)
timeFrame: 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
measure: Vz/F,ss (apparent volume of distribution during the terminal phase λz at steady state following extravascular administration)
timeFrame: 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
measure: RA,Cmax, (calculated as Cmax,ss/Cmax)
timeFrame: 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
measure: RA,AUC, (calculated as AUCτ,ss/AUCτ,1)
timeFrame: 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
measure: linearity index (LI)
timeFrame: 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
Other outcomes:
Locations:
Study officials:
References: