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

Boehringer Ingelheim

Status and phase: Terminated; Phase 1

Conditions: Healthy

Treatments: Drug: Dabigatran etexilate capsules; Drug: Fexofenadine tablets; Drug: Quinidine sulfate tablets

Study type: Interventional

Funder types: Industry

Identifiers

NCT02171546

1160.75

Details and patient eligibility

About

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

Enrollment: 42 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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42 participants in 4 patient groups

Dabigatran etexilate capsules

Active Comparator group

Treatment:

Drug: Dabigatran etexilate capsules

Dabigatran etexilate capsules and quinidine sulfate tablets

Experimental group

Treatment:

Drug: Dabigatran etexilate capsules

Drug: Quinidine sulfate tablets

Fexofenadine tablets

Active Comparator group

Treatment:

Drug: Fexofenadine tablets

Fexofenadine and quinidine sulfate tablets

Experimental group

Treatment:

Drug: Fexofenadine tablets

Drug: Quinidine sulfate tablets