Clinical trial NCT02171052: Relative Bioavailability of Dabigatran and Digoxin in Healthy Male and Female Volunteers
Official title: Relative Bioavailability of Dabigatran and Digoxin After 150 mg BID Dabigatran Etexilate and Digoxin at 0.25 mg QD Alone or Following Concomitant Multiple Oral Administrations in Healthy Male and Female Volunteers (an Open Label, Randomised, Multiple-dose, Three-way Crossover Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-06-23
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: To investigate the bioavailability of dabigatran with and without concomitant administration of digoxin and the bioavailability of digoxin with and without concomitant administration of dabigatran etexilate


Eligibility 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 (BP, PR), 12-lead ECG, clinical laboratory tests
2. Age ≥18 and ≤65 years
3. BMI ≥18.5 and BMI ≤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. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders
2. Relevant surgery of gastrointestinal tract
3. History of any bleeding disorder or acute blood coagulation defect
4. Puls below 50 bpm at screening
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 allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
9. Intake of any medication within four weeks of first dosing.
10. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within four weeks prior to administration or during the trial
11. Participation in another trial with an investigational drug within two months prior to administration or during the trial
12. Alcohol abuse (more than 60 g/day)
13. Drug abuse
14. Within 5 days of study medication no intake of grapefruit, grapefruit juice, or products containing grapefruit juice, Seville oranges, garlic supplements, or St. John's Worth
15. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
16. Excessive physical activities (within one week prior to administration or during the trial)
17. Any laboratory value outside the reference range that is of clinical relevance
18. Inability to comply with dietary regimen of study centre
19. 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
20. Male subjects must agree to minimise the risk of female partners becoming pregnant from the first dosing day until 3 months after the completion of the post study medical. 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)
21. Planned surgeries within four weeks following the end-of study examination
22. Intake of medication, which influences the blood clotting, i.e., acetylsalicylic acid, cumarin etc.
23. The subject is able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
24. Vulnerable subjects (e.g. persons kept in detention).

Primary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma at steady state over a uniform dosing interval τ (AUCτ,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Maximum measured concentration of the analyte in plasma at steady state (Cmax,ss)
timeFrame: 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
Secondary outcomes:
measure: 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)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Time of last measurable concentration of the analyte in plasma within the dosing interval τ at steady state (tz,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Time from last dosing to the maximum concentration of the analyte in plasma at steady state (tmax,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Apparent clearance of the analyte in the plasma at steady state after extravascular multiple dose administration (CL/Fss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Renal clearance of the analyte at steady state determined over the dosing interval τ (CLR,ss)
timeFrame: Up to 24 hours after drug administration on day 4
measure: Minimum measured concentration of the analyte in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval τ ( tmin,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Pre-dose concentration of the analyte in plasma at steady state immediately before administration of the next dose (Cpre,ss)
timeFrame: 2 hours before drug administration on day 4
measure: Mean residence time of the analyte in the body at steady state after p.o. administration (MRTp.o.,ss)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Fraction of parent drug eliminated in urine at steady state over a uniform dosing interval τ (feτ,ss)
timeFrame: Up to 24 hours after drug administration on day 4
measure: Assessment of tolerability by investigator on a four point scale (good, satisfactory, not satisfactory, bad)
timeFrame: Day 76
measure: Apparent volume of distribution during the terminal phase λz at steady state following an extravascular administration (Vz/Fss)
timeFrame: Up to day 7
measure: Amount of analyte that was eliminated in urine at steady state over an uniform dosing interval τ (Aeτ,ss)
timeFrame: Up to 24 hours after drug administration on day 4
measure: Area under the effect ratio curve (AUERτ,ss) for activated prothrombin time (aPTT) and ecarin clotting time (ECT)
timeFrame: Up to 72 hours after drug administration on day 4
measure: Prolongation at trough (ERpre,ss) for aPTT
timeFrame: Up to 72 hours after drug administration on day 4
measure: Change from baseline in physical examination
timeFrame: Baseline, day 76
measure: Change from baseline in vital signs (blood pressure, pulse rate)
timeFrame: Baseline, day 76
measure: Change from baseline in 12-lead electrocardiogram
timeFrame: Baseline, day 76
measure: Change from baseline in clinical laboratory tests
timeFrame: Baseline, day 76
measure: Number of Participants with Serious and Non-Serious Adverse Events
timeFrame: Up to day 76
measure: Maximum effect ratio at steady state (ERmax,ss) for aPTT and ECT
timeFrame: Up to 72 hours after drug administration on day 4
measure: Prolongation at trough (ERpre,ss) for ECT
timeFrame: Up to 72 hours after drug administration on day 4
Other outcomes:
Locations:
Study officials:
References: