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)

Boehringer Ingelheim0 sites28 target enrollmentOctober 2009

ConditionsHealthy

InterventionsDabigatran etexilate low Dabigatran etexilate high

DrugsDabigatran etexilate low Dabigatran etexilate high

Overview

Phase: Phase 1
Intervention: Dabigatran etexilate low
Conditions: Healthy
Sponsor: Boehringer Ingelheim
Enrollment: 28
Primary Endpoint: Changes in physical examination
Status: Completed
Last Updated: 11 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

October 2009

End Date

November 2009

Last Updated

11 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Boehringer Ingelheim

Responsible Party

Sponsor

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/m
•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).

Arms & Interventions

Dabigatran etexilate low

Intervention: Dabigatran etexilate low

Dabigatran etexilate high

Intervention: Dabigatran etexilate high

Outcomes

Primary Outcomes

Changes in physical examination

Time Frame: Day 1 and 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

Changes in vital signs

Time Frame: Day 1 to 14

Occurrence of adverse events

Time Frame: up to 7 days after last drug intake

Secondary Outcomes

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)