Safety, Pharmacodynamics and Pharmacokinetics After Single Oral Administration of Dabigatran Etexilate Capsule in Healthy Subjects

Study Overview
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Brief Summary
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To assess safety, pharmacokinetics and the effect of dabigatran on coagulation parameters prior to administration of a high dose of dabigatran etexilate in a QT study

Official Title
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Safety, Pharmacodynamics and Pharmacokinetics After Single Oral Administration of 600 mg, 750 mg and 900 mg Dabigatran Etexilate as Capsule in Healthy Subjects. A Randomised, Placebo-controlled Study, Double Blind at Each Dose Level

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dabigatran etexilate low dose
* Drug: Dabigatran etexilate medium dose
* Drug: Dabigatran etexilate high dose
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males according to the following criteria: Based upon a complete medical history, including the physical examination, vital signs (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), clinical laboratory tests Age ≥18 and ≤55 years Body Mass Index (BMI) ≥18.5 and BMI ≤29.9 kg/m2 Signed and dated written informed consent prior to admission to the study in accordance with GCP (Good Clinical Practice) and the local legislation. Exclusion Criteria: Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders Relevant surgery of gastrointestinal tract History of any bleeding disorder or acute blood coagulation defect Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders History of relevant orthostatic hypotension, fainting spells or blackouts Chronic or relevant acute infections History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator Intake of drugs with a long half-life (>24 hours) within at least one month or less than 10 half-lives of the respective drug prior to administration or during the trial Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial Participation in another trial with an investigational drug within two months prior to administration or during the trial Alcohol abuse (more than 60 g/day) Drug abuse Blood donation (more than 100 mL within four weeks prior to administration or during the trial) Excessive physical activities (within one week prior to administration or during the trial) Any laboratory value outside the reference range that is of clinical relevance Inability to comply with dietary regimen of study centre

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency [N (%)] of subjects with adverse events |  | up to 18 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (maximum measured concentration of free and total BIBR 953 ZW in plasma) |  | up to 72 hours after administration | 
| tmax (time from dosing to maximum measured concentration) |  | up to 72 hours after administration | 
| AUC0-∞ (area under the concentration-time curve of free and total BIBR 953 ZW in plasma over the time interval from 0 extrapolated to infinity) |  | up to 72 hours after administration | 
| λz (terminal rate constant in plasma) |  | up to 72 hours after administration | 
| t1/2 (terminal half-life of the analyte in plasma) |  | up to 72 hours after administration | 
| MRTpo (mean residence time of the analyte in the body after oral administration) |  | up to 72 hours after administration | 
| CL/F (apparent clearance of the analyte in plasma after extravascular administration) |  | up to 72 hours after administration | 
| Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose) |  | up to 72 hours after administration | 
| Aet1-t2 (amount of analyte eliminated in urine from the time point t1 to time point t2) |  | up to 72 hours after administration | 
| fet1-t2 (fraction of analyte eliminated in urine from time point t1 to time point t2) |  | up to 72 hours after administration | 
| CLR,t1-t2 (renal clearance of the analyte from the time point t1 until the time point t2) |  | up to 72 hours after administration |