Relative Bioavailability of Single Doses of Dabigatran Etexilate When Administered Alone or in Combination With a Single Dose of Ketoconazole or in Combination With q.d. Ketoconazole at Steady State in Healthy Male and Female Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Dabigatran etexilate; Drug: Ketoconazole

Study type: Interventional

Funder types: Industry

Identifiers

NCT02170675

1160.101

Details and patient eligibility

About

To investigate whether and to what extent the P-glycoprotein (P-gp) inhibitor ketoconazole affects plasma exposure of dabigatran.

Enrollment: 24 patients

Sex: All

Ages: 21 to 50 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 ≥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

    Exclusion criteria that were specific for this study:

18. Intake of medication, which influences the blood clotting, such as acetylsalicylic acid and oral vitamin K antagonists

    For female subjects:

19. Pregnancy / positive pregnancy test, or planning to become pregnant during the study or within 1 month of study completion

20. No adequate contraception during the study and until 1 month of study completion, i.e.

    implants, injectables, combined oral contraceptives, IUD [intrauterine device], sexual abstinence (for at least 1 month prior to enrolment), or surgical sterilisation (incl.

    hysterectomy). Females, who were not surgically sterile were asked to additionally use barrier contraception methods (e.g. condom, diaphragm with spermicide)

21. Lactation period

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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24 participants in 1 patient group

Dabigatran etexilate + Ketoconazole

Experimental group

Description:

Period 1 - Dabigatran etexilate Period 2 - Dabigatran etexilate and single dose of 400 mg Ketoconazole on Day 8 and 9 Period 3 - Dabigatran etexilate and multiple doses of 400 mg Ketoconazole on Day 10 to 16

Treatment:

Drug: Dabigatran etexilate

Drug: Ketoconazole