Relative Bioavailability of Single Oral Doses of Dabigatran Etexilate With or Without Oral Administration of Verapamil in Two Different Dosages in Healthy Male and Female Volunteers

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Verapamil ER; Drug: dabigatran; Drug: Verapamil

Study type: Interventional

Funder types: Industry

Identifiers

NCT02171533

1160.74

Details and patient eligibility

About

To investigate whether and to what extent the P-glycoprotein inhibitor (P-gp) verapamil affects the pharmacokinetic parameters of dabigatran with verapamil given at different dosages, in different formulations (immediate release (IR) and extended release (ER)), and in different intervals in relation to the dabigatran dose.

Enrollment: 40 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 (blood pressure (BP), pulse rate (PR)), 12-lead electrocardiogram (ECG), 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 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. 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 trial as judged by the investigator

8. Pulse rate below 50 bpm and or systolic blood pressure <90 mm Hg at screening. ECG: PR >170 ms (Part 1), AV block ≥1st degree (Part 2) at screening

9. 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, especially intake of medication, which influences the blood clotting, i.e., acetylsalicylic acid, cumarin etc.

10. Participation in another trial with an investigational drug within two months prior to administration or during the trial

11. Smoker (more than 15 cigarettes or 3 cigars or 3 pipes per day)

12. Alcohol abuse (more than 60 g/day for men and more than 40 g/day for women)

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 is of clinical relevance

17. Planned surgeries within four weeks following the end-of study examination

18. The subject is not able to understand and comply with protocol requirements, instructions, protocol-stated restrictions and dietary regimen of study centre

    For male subjects:

19. Male subjects who do not 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)

    For female subjects:

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

21. 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), vasectomised partner (vasectomy performed at least 1 year prior to enrolment), or surgical sterilisation (incl. hysterectomy). Females, who have not a vasectomised partner, are not sexually abstinent or surgically sterile will be asked to additionally use barrier contraception methods (e.g. condom, diaphragm with spermicide)

22. Lactation period

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

---

40 participants in 2 patient groups

Fixed sequence

Experimental group

Description:

Treatments will be given in a fixed sequence

Treatment:

Drug: Verapamil

Drug: dabigatran

Crossover

Experimental group

Description:

Treatments will be given in randomized sequences

Treatment:

Drug: Verapamil ER

Drug: Verapamil

Drug: dabigatran