Relative Bioavailability of Dabigatran and Diclofenac After Dabigatran Etexilate and Diclofenac Single Dose Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers
Information source: Boehringer Ingelheim
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Dabigatran etexilate (Drug); Diclofenac (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Boehringer Ingelheim
Summary
To investigate the relative bioavailability of dabigatran with and without concomitant
administration of diclofenac and the relative bioavailability of diclofenac with and without
concomitant administration of dabigatran etexilate
Clinical Details
Official title: Relative Bioavailability of Dabigatran and Diclofenac After 150 mg b.i.d. Dabigatran Etexilate and Diclofenac at 50 mg Single Dose Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers (an Open Label, Randomised, Multiple- Dose, Three-way Crossover Study)
Study design: Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: AUCτ,ss on Day 4 (area under the concentration-time curve of dabigatran in plasma at steady state over one dosing interval)Cmax,ss (maximum concentration of dabigatran in plasma at steady state) Cmax (maximal concentration of diclofenac in plasma) AUC0-infinity (area under the concentration-time curve of diclofenac in plasma extrapolated to infinity) aPTT (activated partial thromboplastin time) and ECT (Ecarin clotting time) with and without diclofenac AUERτ,ss (area under the effect ratio-time curve of dabigatran in plasma at steady state over a uniform dosing interval τ) ERmax,ss (maximal effect ratio of dabigatran in plasma at steady state)
Secondary outcome: AUC0-tz,ss (area under the concentration-time curve of dabigatran in plasma from the time point 0 after the last dose at steady state to the last quantifiable dabigatran plasma concentration within the uniform dosing interval τ)tz,ss (time of last measurable concentration of dabigatran in plasma within the dosing interval τ at steady state) tmax,ss (time from last dosing to the maximum concentration of dabigatran in plasma at steady state on Day 4) CL/Fss (apparent clearance of dabigatran in the plasma at steady state after extravascular multiple dose administration) CLR,ss (renal clearance of dabigatran at steady state determined over the dosing interval τ) C min,ss (minimum measured concentration of dabigatran in plasma at steady state over a uniform dosing interval τ) tmin,ss (time from last dosing to the minimum concentration of dabigatran in plasma at steady state over a uniform dosing interval τ) Cpre,ss (pre-dose concentration of dabigatran in plasma at steady state immediately before administration of the next dose) MRTp.o.,ss (mean residence time of dabigatran in the body at steady state after oral administration) Vz/Fss (apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration) Aeτ,ss (amount of dabigatran that is eliminated in urine at steady state over a uniform dosing interval τ) feτ,ss (fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ) AUC0-tz (area under the concentration-time curve of diclofenac and 4´- hydroxydiclofenac in plasma over the time interval 0 to the last quantifiable analyte plasma concentration after single dose administration) tz (time of last measurable concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose) %AUCtz-infinity (percentage of the AUC0-infinity that is obtained by extrapolation) for diclofenac and 4´- hydroxydiclofenac tmax (time from dosing to the maximum concentration of diclofenac and 4´- hydroxydiclofenac in plasma following a single dose) λz (terminal rate constant in plasma after a single dose) for diclofenac and 4´- hydroxydiclofenac t1/2 (terminal half-life of diclofenac and 4´- hydroxydiclofenac in plasma after a single dose) MRTp.o. (mean residence time of diclofenac and 4´- hydroxydiclofenac in the body after single dose oral administration) CL/F (apparent clearance of diclofenac and 4´- hydroxydiclofenac in the plasma after extravascular single dose administration) Vz/F (apparent volume of distribution during the terminal phase λz following extravascular dose) for diclofenac and 4´- hydroxydiclofenac
Eligibility
Minimum age: 18 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
Inclusion criteria:
1. Healthy males and females according to the following criteria: Based upon a complete
medical history, including the physical examination, vital signs (blood pressure,
pulse rate), 12-lead electrocardiogram, clinical laboratory tests
2. Age ≥18 and ≤55 years
3. Body mass index (BMI) ≥18. 5 and BMI ≤29. 9 kg/m2
4. 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:
1. Clinically relevant gastrointestinal, hepatic, renal, respiratory, cardiovascular,
metabolic, immunological or hormonal disorders
2. Relevant surgery of gastrointestinal tract
3. History of any bleeding disorder including history of gastrointestinal erosions and
ulcer or acute blood coagulation defect
4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or
neurological disorders
5. History of relevant orthostatic hypotension, fainting spells or blackouts
6. Chronic or relevant acute infections
7. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant
to the objectives of the trial as judged by the investigator
8. 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
9. 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
10. Participation in another trial with an investigational drug within two months prior
to administration or during the trial
11. Alcohol abuse (more than 60 g/day)
12. Drug abuse
13. Blood donation (more than 100 mL within four weeks prior to administration or during
the trial)
14. Excessive physical activities (within one week prior to administration or during the
trial)
15. Any laboratory value outside the reference range that is of clinical relevance
16. Subjects with abnormal thrombocyte counts and any relevant deviation in the
assessment of platelet function (PFA test) must be excluded
17. Inability to comply with dietary regimen of study centre
18. Females of child bearing potential who are pregnant, breast feeding or who are either
not surgically sterile or are sexually active and not using an acceptable form of
contraception as either the oral contraceptives since at least two months and the
double barrier method, i. e. intrauterine device with spermicide and condom for the
male partner
19. Male subjects must agree to minimize the risk of female partners becoming pregnant
from the first dosing day until 3 months after the completion of the post study
medical examination. Acceptable methods of contraception comprises barrier
contraception and a medically accepted contraceptive method for the female partner
(intra-uterine device with spermicide, hormonal contraceptive since at least two
month)
20. Planned surgeries within four weeks following the end-of study examination
21. Intake of medication, which influences the blood clotting, i. e., acetylsalicylic
acid, cumarin etc.
22. The subject is able to understand and comply with protocol requirements, instructions
and protocol-stated restrictions
23. Vulnerable subjects (e. g. persons kept in detention).
Locations and Contacts
Additional Information
Starting date: May 2006
Last updated: June 20, 2014
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