Clinical trial NCT02264041: Effect of Cytochrome P 450 3A4 Inhibition by Itraconazole on the Single Oral Dose Pharmacokinetics of Cilobradine
Official title: The Effect of Cytochrome P 450 3A4 Inhibition by Itraconazole on the Single Oral Dose Pharmacokinetics of Cilobradine (an Open-label, Randomised, Single-dose, Two-way Crossover Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 25
Sex: MALE
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Maximum measured concentration of the analyte in plasma (Cmax)
timeFrame: up to 56 hours after administration of Cilobradine
Secondary outcomes:
measure: Area under the concentration-time curve of the analyte in plasma over the time interval from 0 to the time of the last quantifiable data point (AUC0-tz)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Time from dosing to Cmax (Tmax)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Terminal rate constant in plasma (λz)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Terminal half-life of the analyte in plasma (t1/2)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Mean residence time of the analyte in the body after p.o. administration (MRTpo)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Apparent clearance of the analyte in the plasma after extravascular administration (CL/F)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
timeFrame: up to 56 hours after administration of Cilobradine
measure: Amount of parent compound excreted in urine with zero to 72 h in % of dose (fe0-tz)
timeFrame: up to 72 hours after administration of Cilobradine
measure: Renal clearance of cilobradine (CLR,0-tz)
timeFrame: up to 72 hours after administration of Cilobradine
measure: Number of subjects with adverse events
timeFrame: up to 46 days
measure: Occurrence of visual phenomena
timeFrame: up to 46 days
measure: Number of subjects with clinically relevant findings in vital signs
timeFrame: up to 32 days
measure: Number of subjects with clinically relevant findings in laboratory tests
timeFrame: up to 32 days
measure: Number of subjects with clinically relevant findings in 12-lead electrocardiogram
timeFrame: up to 32 days
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: within 8 days after last PK sampling
Other outcomes:
Locations:
Study officials:
References: