Relative Bioavailability of Dabigatran Etexilate Capsules With and Without Quinidine Sulfate Tablets and to Measure the Effect of Quinidine on the Absorption of Fexofenadine in Healthy Male and Female Volunteers

Phase 1TerminatedNCT02171546

Boehringer Ingelheim42 enrolled

Overview

Part 1: To investigate the effect of quinidine, a P-glycoprotein (P-gp) probe inhibitor on the bioavailability of dabigatran etexilate, Part 2: To determine the effect of quinidine on the bioavailability of fexofenadine, a probe substrate for P-gp

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Dabigatran etexilate capsulesDRUG

Quinidine sulfate tabletsDRUG

Fexofenadine tabletsDRUG

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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 Age ≤55 years; 3. Body Mass Index (BMI) ≥18.5 and BMI \<30 kg/m2; 4. Signed and dated written informed consent prior to admission to the study in accordance with GCP and the local legislation; 5. If female of child-bearing potential, not be pregnant or breast feeding, nor plan to become pregnant for the duration of the study and for 2 months after receiving the last dose of study drug, and have a negative serum pregnancy test within 14 days of treatment, and prior to dosing; 6. Females of child-bearing potential willing to use adequate contraception, defined as the use of hormonal (oral, injectable or implantable) or barrier method contraceptives, intrauterine device and agree to use the same method of contraception for at least 2 months after drug administration. Women who have undergone a total hysterectomy, have a history of bilateral tubal ligation or are at least 2 years post-menopausal are not considered to be of child-bearing potential. 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; 10. Use of drugs which might reasonably influence the results of the trial or that prolong the QT/QTc interval based on the knowledge at the time of protocol preparation within 10 days 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. Smoker (\>10 cigarettes or \>3 cigars or \>3 pipes/day); 13. Inability to refrain from smoking on trial days; 14. Alcohol abuse (more than 60 g/day); 15. Drug abuse; 16. Blood donation (more than 100 mL within four weeks prior to administration or during the trial); 17. Excessive physical activities (within one week prior to administration or during the trial); 18. Any laboratory value outside the reference range that is of clinical relevance; 19. Inability to comply with dietary regimen of trial site; 20. A marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 ms); 21. A history of additional risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome); 22. Taking drugs which are known P-gp inhibitors or inducers (verapamil, phenothiazine antipsychotics, erythromycin, antifungal drugs or St. John´s Wort) within the last 4 weeks before screening; 23. Chronic use of oral contraception containing ethinyl estradiol as the only method of contraception.

Outcomes

Primary Outcomes

AUCτ,ss (area under the concentration-time curve of dabigatran in plasma at steady state over one dosing interval)

Time frame: Before dose, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00 and 12:00 hours after dosing on day 3

Cmax,ss (maximum concentration of dabigatran in plasma at steady state)

Time frame: Before dose on day 1, day 2, before dose, 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 48:00 hours after dosing on Day 3

AUC0-∞ (area under the concentration-time curve of fexofenadine in plasma over the time interval from 0 to infinity)

Time frame: Before dose, 0:30, 1:00,1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 48:00 hours after dosing on day 1

Cmax (maximum measured concentration of fexofenadine in plasma)

Time frame: Before dose, 0:30, 1:00,1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24:00 and 48:00 hours after dosing on day 1

Secondary Outcomes

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)

Time frame: 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24 and 48 hours after dosing on day 3

tz,ss (time of last measurable concentration of dabigatran in plasma within the dosing interval τ at steady state)

Time frame: 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24 and 48 hours after dosing on day 3

tmax,ss (time from last dosing to the maximum concentration of dabigatran in plasma at steady state)

Time frame: 0:30, 1:00, 1:30, 2:00, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00, 24 and 48 hours after dosing on day 3

Data from ClinicalTrials.gov

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