Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02264041
Recruitment Status : Completed
First Posted : October 15, 2014
Last Update Posted : October 15, 2014
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

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

Condition or disease Intervention/treatment Phase
Healthy Drug: Cilobradine, low dose Drug: Cilobradine, high dose Drug: Itraconazole Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : January 2004
Actual Primary Completion Date : April 2004

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cilobradine, low dose plus itraconazole
Pre-study
Drug: Cilobradine, low dose
Drug: Itraconazole
Other Name: Sempera®

Active Comparator: Cilobradine, low dose
Pre-study
Drug: Cilobradine, low dose
Experimental: Cilobradine, high dose plus itraconazole
main study
Drug: Cilobradine, high dose
Drug: Itraconazole
Other Name: Sempera®

Active Comparator: Cilobradine, high dose
main study
Drug: Cilobradine, high dose



Primary Outcome Measures :
  1. Area under the concentration-time curve of the analyte in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  2. Maximum measured concentration of the analyte in plasma (Cmax) [ Time Frame: up to 56 hours after administration of Cilobradine ]

Secondary Outcome Measures :
  1. 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) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  2. Time from dosing to Cmax (Tmax) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  3. Terminal rate constant in plasma (λz) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  4. Terminal half-life of the analyte in plasma (t1/2) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  5. Mean residence time of the analyte in the body after p.o. administration (MRTpo) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  6. Apparent clearance of the analyte in the plasma after extravascular administration (CL/F) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  7. Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F) [ Time Frame: up to 56 hours after administration of Cilobradine ]
  8. Amount of parent compound excreted in urine with zero to 72 h in % of dose (fe0-tz) [ Time Frame: up to 72 hours after administration of Cilobradine ]
  9. Renal clearance of cilobradine (CLR,0-tz) [ Time Frame: up to 72 hours after administration of Cilobradine ]
  10. Number of subjects with adverse events [ Time Frame: up to 46 days ]
  11. Occurrence of visual phenomena [ Time Frame: up to 46 days ]
    questionnaire

  12. Number of subjects with clinically relevant findings in vital signs [ Time Frame: up to 32 days ]
    blood pressure, pulse rate

  13. Number of subjects with clinically relevant findings in laboratory tests [ Time Frame: up to 32 days ]
  14. Number of subjects with clinically relevant findings in 12-lead electrocardiogram [ Time Frame: up to 32 days ]
  15. Assessment of tolerability by investigator on a 4-point scale [ Time Frame: within 8 days after last PK sampling ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 55 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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

Additional Information:
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT02264041     History of Changes
Other Study ID Numbers: 503.213
First Posted: October 15, 2014    Key Record Dates
Last Update Posted: October 15, 2014
Last Verified: October 2014

Additional relevant MeSH terms:
Layout table for MeSH terms
Itraconazole
Hydroxyitraconazole
Antifungal Agents
Anti-Infective Agents
14-alpha Demethylase Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Steroid Synthesis Inhibitors
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Cytochrome P-450 CYP3A Inhibitors