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To investigate the relative bioavailability and the pharmacodynamics of dabigatran after switching from enoxaparin to dabigatran etexilate as compared to dabigatran etexilate alone
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dabigatran etexilate capsules after enoxaparin ampoules | Experimental |
| |
| Dabigatran etexilate capsules without enoxaparin | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Enoxaparin prefilled syringes | Drug |
| ||
| Dabigatran etexilate capsules |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) of dabigatran | Up to 48 hours after drug administration | |
| Maximum measured concentration of the analyte in plasma (Cmax ) of dabigatran | Up to 48 hours after drug administration | |
| Area under the effect-time curve of the analyte in plasma over the time interval from 0 to 48 h after administration (AUEC0-48) after dabigatran alone and after dabigatran following enoxaparin administration | Up to 48 hours after drug administration | |
| Maximum effect ratio to baseline (ERmax) after dabigatran alone and after dabigatran following enoxaparin administration | Baseline and up to 48 hours after drug administration |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the last quantifiable data point (AUC0-tz) of dabigatran | Up to 48 hours after drug administration | |
| Time from dosing to the maximum concentration of the analyte in plasma (tmax) of dabigatran |
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Inclusion Criteria:
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 was deemed relevant to the trial as judged by the investigator
Intake of any medication within 2 weeks of first dosing, especially intake of medication, which influences blood clotting, i.e. acetylsalicylic acid, cumarin etc.
Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 4 weeks prior to administration or during the trial
Alcohol abuse (more than 60 g/day for males and more than 20 g/day for females)
Drug abuse
Intake of grapefruit, grapefruit juice, or products containing grapefruit juice, Seville oranges, garlic supplements, or St. John's wort within 5 days of first dosing
Participation in another trial with an investigational drug within 2 months prior to trial drug administration or during the trial
Blood donation (more than 100 mL within 4 weeks prior to trial drug administration or during the trial)
Excessive physical activities (within 1 week prior to trial drug administration or during the trial)
Any laboratory value outside the reference range that was of clinical relevance
Inability to comply with dietary regimen of study centre
Smoker (>10 cigarettes or >3 cigars or >3 pipes/day)
Inability to refrain from smoking on trial days
For female subjects:
Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month after study completion
No adequate contraception during the study and within 1 month after study completion such as implants, injectables, combined oral contraceptives, intrauterine device, sexual abstinence (for at least 1 month prior to enrolment), vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (including hysterectomy). Females, who did not have a vasectomised partner, were not sexually abstinent or surgically sterile, were asked to additionally use a barrier contraception method (e.g. condom, diaphragm with spermicide)
Lactation period
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| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
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| Drug |
|
| Up to 48 hours after drug administration |
| Terminal rate constant in plasma (λz) of dabigatran | Up to 48 hours after drug administration |
| Terminal half-life of the analyte in plasma (t1/2) of dabigatran | Up to 48 hours after drug administration |
| Mean residence time of the analyte in the body after oral administration (MRTpo) of dabigatran | Up to 48 hours after drug administration |
| Apparent clearance of the analyte in plasma after extravascular administration (CL/F) of dabigatran | Up to 48 hours after drug administration |
| Apparent volume of distribution during the terminal phase λz following an extravascular administration (Vz/F) of dabigatran | Up to 48 hours after drug administration |
| Anti-FIIa activity for Dabigatran etexilate | Up to 48 hours after drug administration |
| Anti-FXa/anti-FIIa activity for Enoxaparin | Up to 48 hours after drug administration |
| Activated partial thromboplastin time (aPTT) for Dabigatran etexilate | Up to 48 hours after drug administration |
| Ecarin clotting time (ECT) for Dabigatran etexilate | Up to 48 hours after drug administration |
| Thrombin time (TT) for Dabigatran etexilate | Up to 48 hours after drug administration |
| Change in vital signs (blood pressure, pulse rate) | up to day 61 |
| Change in 12-lead electrocardiogram (ECG) | up to day 61 |
| Change in clinical laboratory tests | up to day 61 |
| Occurrence of adverse events | Up to day 61 |
| Assessment of global tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad) | Day 61 |
| Assessment of local tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad) | day 3 of enoxaparin administration |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |