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Study to Investigate the Effect of Ketoconazole Mediated CYP3A4 Inhibition on Pharmacokinetics of Tamsulosin in Healthy Male Volunteers

Phase 1
Completed
Conditions
Healthy
Interventions
Registration Number
NCT02264171
Lead Sponsor
Boehringer Ingelheim
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

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
24
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
Tamsulosin HClTamsulosin HClTamsulosin HCl given at day 1
Ketoconazole + Tamsulosin HClTamsulosin HClKetoconazole given once daily in the morning on days -3 to 2 Tamsulosin HCl given at day 1
Ketoconazole + Tamsulosin HClKetoconazoleKetoconazole given once daily in the morning on days -3 to 2 Tamsulosin HCl given at day 1
Primary Outcome Measures
NameTimeMethod
Cmax (maximum measured concentration of Tamsulosin HCl in plasma)up to 48 hours after dosing
AUC0-∞ (Area under the concentration-time curve of Tamsulosin HCl in plasma over the time interval from 0 extrapolated to infinity)up to 48 hours after dosing
Secondary Outcome Measures
NameTimeMethod
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)up to 48 hours after dosing
CL/F (apparent clearance of the analyte in the plasma after extravascular administration)up to 48 hours after dosing
Ratio of the Cmax value of the Test treatment to the Cmax value of the Reference treatment after single dose (RCmax,T/R)up to 48 hours after dosing
tmax (time from dosing to the maximum concentration of Tamsulosin HCl in plasma)up to 48 hours after dosing
λz (terminal rate constant of Tamsulosin HCl in plasma)up to 48 hours after dosing
Vz/F (apparent volume of distribution of Tamsulosin HCl during the terminal phase λz following an extravascular dose)up to 48 hours after dosing
Number of subjects with adverse eventsup to 21 days after last Tamsulosin administration
MRTpo (mean residence time Tamsulosin HCl in the body after oral administration)up to 48 hours after dosing
Assessment of tolerability by investigator on a 4-point scalewithin 21 days after last Tamsulosin administration
t1/2 (terminal half-life of Tamsulosin HCl in plasma)up to 48 hours after dosing
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)up to 48 hours after dosing
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