Effect of Cytochrome P 450 3A4 Inhibition by Itraconazole on the Single Oral Dose Pharmacokinetics of Cilobradine

Boehringer Ingelheim

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Drug: Itraconazole; Drug: Cilobradine, high dose; Drug: Cilobradine, low dose

Study type: Interventional

Funder types: Industry

Identifiers

NCT02264041

503.213

Details and patient eligibility

About

Study to investigate the effect of cytochrome P 450 3A4 inhibition by itraconazole on the single dose pharmacokinetics of cilobradine

Enrollment: 25 patients

Sex: Male

Ages: 21 to 55 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Healthy males 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

   1.1 No finding deviating from normal and of clinical relevance

   1.2 No evidence of a clinically relevant concomitant disease

2. Age ≥21 and Age ≤55 years

3. BMI ≥18.5 and BMI < 30 kg/m2 (Body Mass Index)

4. Resting pulse rate (PR; after 10 min. in the supine position) of more than 55 bpm

5. Signed and dated written informed consent prior to admission to the study in accordance with Good Clinical Practice and the local legislation

Exclusion criteria

1. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological, ophthalmological, or hormonal disorders
2. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
3. History of relevant orthostatic hypotension, fainting spells or blackouts.
4. Chronic or relevant acute infections
5. History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
6. 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
7. Use of drugs which might reasonably influence the results of the trial based on the knowledge at the time of protocol preparation within 10 days prior to administration or during the trial.
8. Participation in another trial with an investigational drug within two months prior to administration or during the trial
9. Smoker (more than 10 cigarettes or 3 cigars or 3 pipes/day)
10. Inability to refrain from smoking on trial days
11. Alcohol abuse (more than 60 g/day)
12. Drug abuse
13. Blood donation (more than 100 mL within four weeks prior to administration or during the trial)
14. Excessive physical activities (within one week prior to administration or during the trial)
15. Any laboratory value outside the reference range that is of clinical relevance

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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25 participants in 4 patient groups

Cilobradine, low dose plus itraconazole

Experimental group

Description:

Pre-study

Treatment:

Drug: Cilobradine, low dose

Drug: Itraconazole

Cilobradine, low dose

Active Comparator group

Description:

Pre-study

Treatment:

Drug: Cilobradine, low dose

Cilobradine, high dose plus itraconazole

Experimental group

Description:

main study

Treatment:

Drug: Cilobradine, high dose

Drug: Itraconazole

Cilobradine, high dose

Active Comparator group

Description:

main study

Treatment:

Drug: Cilobradine, high dose