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To investigate the bioavailability of dabigatran with and without concomitant administration of atorvastatin and the bioavailability of atorvastatin with and without concomitant administration of dabigatran etexilate
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dabigatran plus atorvastatin | Experimental |
| |
| dabigatran | Active Comparator |
| |
| atorvastatin | Active Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dabigatran | Drug |
| ||
| Atorvastatin |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve of the analyte in plasma at steady state over one dosing interval ( AUCτ,ss) | Day 4 | |
| Maximum concentration of the analyte in plasma at steady state (Cmax,ss) | 2 hours before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration on day 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve of the analyte in plasma from the time point 0 after the last dose at steady state to the last quantifiable analyte plasma concentration within the uniform dosing interval τ (AUC0-tz,ss) | Up to day 7 after administration | |
| Time of last measurable concentration of the analyte in plasma within the dosing interval τ at steady state (tz,ss) |
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Inclusion Criteria:
Healthy males and females according to the following criteria:
Based upon a complete medical history, including the physical examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory tests
Age ≥18 and ≤65 years
BMI ≥18.5 and BMI ≤29.9 kg/m2 (Body Mass Index)
Liver transaminases (ALT; aspartate aminotransferase (AST); GGT) and creatin kinase (CK) are to be within the normal range
Haemoglobin values within the normal range
Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion Criteria:
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| ID | Term |
|---|---|
| D000069604 | Dabigatran |
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001562 | Benzimidazoles |
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| Drug |
|
| Up to day 7 after administration |
| Time from last dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss) | Up to day 7 after administration |
| Apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration (CL/Fss) | Up to day 7 after administration |
| Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss) | 2 hours before and 0,5, 1, 1,5, 2, 3, 4, 6, 8, 12, 24, 48 and 72 hours after drug administration |
| Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ (tmin,ss ) | Up to day 7 after administration |
| Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss) | 2 hours before drug administration on day 1, 2, 3 and 4 |
| Mean residence time of the analyte in the body at steady state after p.o. administration (MRTp.o.,ss) | Up to day 7 after administration |
| Apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration (Vz/Fss) | Up to day 7 after administration |
| Amount of analyte that was eliminated in urine at steady state over an uniform dosing interval τ (Aeτ,ss) | Day 4 and 5 after administration |
| Fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ (feτ,ss) | Day 4 and 5 after administration |
| Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss) | Day 4 and 5 after administration |
| Maximum effect ratio at steady state (ERmax_ss) for activated thrombin time (aPTT) and ecarin clotting time (ECT) | Up to day 7 after administration |
| Area under the effect curve (baseline corrected) (AUECτ,ss) for aPTT and ECT | Day 4 and 5 |
| Change from baseline in blood pressure and puls rate (BP, PR) | Baseline, day 78 |
| Change from baseline in physical examination | Baseline, day 78 |
| Change from baseline in 12-lead electrocardiogram | Baseline, day 78 |
| Change from baseline in clinical laboratory tests | Baseline, day 78 |
| Number of Participants with Serious and Non-Serious Adverse Events | Up to day 78 |
| Assessment of tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad) | Day 78 |
| Ecarin clotting time (ECT) prolongation at trough (ER(pre,ss)) | Up to day 7 after administration |
| Amount of total active HMG-CoA reductase inhibitors in plasma | Up to day 7 after administration |
| Activated partial thromboplastin time (aPTT) prolongation at trough (ER(pre,ss)) | Up to day 7 after administration |
| D006574 |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006538 | Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |