Clinical trial NCT02264171: Study to Investigate the Effect of Ketoconazole Mediated CYP3A4 Inhibition on Pharmacokinetics of Tamsulosin in Healthy Male Volunteers
Official title: An Open Label Randomized Two-way Crossover Study to Investigate the Effect of Ketoconazole Mediated CYP3A4 Inhibition on the Single Oral Dose Pharmacokinetics of Tamsulosin in Healthy Male Volunteers (CYP2D6 Extensive Metabolizers)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2014-10-15
Enrollment: 24
Sex: MALE
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Study to investigate the effect of CYP3A4 inhibition by ketoconazole on the single oral dose pharmacokinetics of tamsulosin and to investigate the effect on safety and tolerability


Eligibility criteria: Inclusion Criteria:

All participants in the study will be

* Healthy males
* Ranging from 21 to 50 years of age
* Body mass index (BMI) within 18.5 to 29.9 kg/m2 (BMI calculation: weight in kilograms divided by the square of height in meters)
* In accordance with Good Clinical Practice (GCP) and the local legislation all volunteers will have given their written informed consent prior to admission to the study

Exclusion Criteria:

* Any finding of the medical examination (including blood pressure, pulse rate and ECG) deviating from normal and of clinical relevance
* Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunological or hormonal disorders, clinically relevant electrolyte disturbances
* Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or neurological disorders
* History of orthostatic hypotension, fainting spells or blackouts
* Chronic or clinically relevant acute infections
* History of allergy/hypersensitivity (including drug allergy) which is deemed relevant to the trial as judged by the investigator
* Intake of drugs with a long half-life (\> 24:00 hours) within at least one month or less than ten half-lives of the respective drug before enrolment in the study or during the study
* Use of any drugs which might influence the results of the trial up to 7 days prior to enrolment in the study or during the study
* Participation in another trial with an investigational drug (within two months prior to administration or during the trial)
* Smoker (\> 10 cigarettes or \> 3 cigars of \> 3 pipes/day)
* Inability to refrain from smoking on trial days
* Alcohol abuse (\> 60 g/day)
* Drug abuse
* Blood donation (\> 100 mL within four weeks prior to administration or during the trial)
* Any laboratory value outside the reference range if indicative of underlying disease or poor health
* Excessive physical activities within the last week before the trial or during the trial
* Hypersensitivity to treatment medication and/or related drugs of these classes
* Non extensive metabolizer (EM) for CYP2D6

Primary outcomes:
measure: Cmax (maximum measured concentration of Tamsulosin HCl in plasma)
timeFrame: up to 48 hours after dosing
measure: AUC0-∞ (Area under the concentration-time curve of Tamsulosin HCl in plasma over the time interval from 0 extrapolated to infinity)
timeFrame: up to 48 hours after dosing
Secondary outcomes:
measure: tmax (time from dosing to the maximum concentration of Tamsulosin HCl in plasma)
timeFrame: up to 48 hours after dosing
measure: AUC0-tz (area under the concentration-time curve of Tamsulosin HCl in plasma over the time interval from 0 to the last quantifiable data point)
timeFrame: up to 48 hours after dosing
measure: λz (terminal rate constant of Tamsulosin HCl in plasma)
timeFrame: up to 48 hours after dosing
measure: t1/2 (terminal half-life of Tamsulosin HCl in plasma)
timeFrame: up to 48 hours after dosing
measure: MRTpo (mean residence time Tamsulosin HCl in the body after oral administration)
timeFrame: up to 48 hours after dosing
measure: CL/F (apparent clearance of the analyte in the plasma after extravascular administration)
timeFrame: up to 48 hours after dosing
measure: Vz/F (apparent volume of distribution of Tamsulosin HCl during the terminal phase λz following an extravascular dose)
timeFrame: up to 48 hours after dosing
measure: Number of subjects with adverse events
timeFrame: up to 21 days after last Tamsulosin administration
measure: Assessment of tolerability by investigator on a 4-point scale
timeFrame: within 21 days after last Tamsulosin administration
measure: Ratio of the Cmax value of the Test treatment to the Cmax value of the Reference treatment after single dose (RCmax,T/R)
timeFrame: up to 48 hours after dosing
measure: Ratio of the Test treatment versus the Reference treatment from zero to infinity, expressed as ratio of AUC values after single dose (RAUC0-∞,T/R)
timeFrame: up to 48 hours after dosing
Other outcomes:
Locations:
Study officials:
References: