Healthy
Conditions
Brief summary
To investigate whether and to what extent the P-glycoprotein (P-gp) inhibitor ketoconazole affects plasma exposure of dabigatran.
Interventions
DRUGDabigatran etexilate
DRUGKetoconazole
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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 2. Age ≥21 and ≤50 years 3. BMI range ≥18.5 and ≤29.9 kg/m2 (Body Mass Index) 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation.
Exclusion criteria
1. Any finding of the medical examination (including BP, PR and ECG) deviating from normal and of clinical relevance 2. Any evidence of a clinically relevant concomitant disease 3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders 4. Surgery of the gastrointestinal tract (except appendectomy) 5. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders 6. History of relevant orthostatic hypotension, fainting spells or blackouts. 7. Chronic or relevant acute infections 8. History of relevant allergy/hypersensitivity (including allergy to drug or its excipients) 9. 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, and intake of drugs which might reasonably influence the results of the trial within four weeks prior to administration or during the trial (e.g. P-gp inducers) 10. Participation in another trial with an investigational drug within two months prior to administration or during the trial 11. Smoker (\> 10 cigarettes or \> 3 cigars or \> 3 pipes/day) 12. Alcohol abuse (more than 60 g/day) 13. Drug abuse 14. Blood donation (more than 100 mL within four weeks prior to administration or during the trial) 15. Excessive physical activities (within one week prior to administration or during the trial) 16. Any laboratory value outside the reference range that was of clinical relevance 17. Inability to comply with dietary regimen of trial site
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for total dabigatran | up to Day 16 |
| Maximum measured concentration of the analyte in plasma for total dabigatran | up to Day 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum measured concentration of the analyte in plasma for dabigatran and BIBR 1087 SE, BIBR 951 BS | up to Day 16 | — |
| Time from dosing to the maximum concentration of the analyte in plasma for dabigatran and BIBR 1087 SE, BIBR 951 BS | up to Day 16 | — |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Area under the concentration-time curve of the analyte in plasma over the time interval from timepoints t1 to t2 for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to 24 h for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Time from dosing to the maximum concentration of the analyte in plasma for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Terminal rate constant of the analyte in plasma for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Terminal half-life of the analyte in plasma for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity for free dabigatran | up to Day 16 | — |
| Apparent clearance of the analyte in the plasma after extravascular administration for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Apparent volume of distribution during the terminal phase λz following an extravascular dose for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Changes from baseline in Vital signs (blood pressure [BP], pulse rate) | up to 14 days after last drug administration | — |
| Changes from baseline in 12-lead ECG | up to 14 days after last drug administration | — |
| Changes from baseline in Clinical laboratory tests (haematology, clinical chemistry, and urinalysis) | up to 14 days after last drug administration | — |
| Number of patients with adverse events | up to 14 days after last drug administration | — |
| Assessment of tolerability by the investigator | up to 14 days after last drug administration | — |
| Mean residence time of the analyte in the body after oral administration for dabigatran | up to Day 16 | Dabigatran after each single dose (free and total after conjugate cleavage) |
| Maximum measured concentration of the analyte in plasma for free dabigatran | up to Day 16 | — |
Outcome results
None listed