Clinical trial NCT01386593: Pharmacokinetic Study to Characterize Phenotyping Metrics of the "Basel" Cocktail After CYP Induction or Inhibition
Official title: Single-center, Randomized, Open-label, Two-way Crossover Study to Characterize Phenotyping Metrics of the "Basel" Cocktail After CYP Induction or Inhibition in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Metabolic Detoxication, Phase I
Keywords: Cytochrome
Phenotyping
Pharmacokinetics
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2011-07-01
Enrollment: 16
Sex: MALE
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The purpose of this study is to assess how the pharmacokinetic profiles of each drug of a cocktail of six approved drugs (so-called "Basel cocktail") change when the cytochrome P450 system is inhibited or induced.


Eligibility criteria: Inclusion Criteria:

* Male aged between 18 and 35 years (inclusive) at screening.
* No clinically significant findings on the physical examination at screening.
* Body mass index (BMI) between 18 and 28 kg/m2 (inclusive) and body weight at least 50 kg at screening.
* Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg and heart rate (HR) 45-90 bpm (inclusive).
* 12-lead electrocardiogram (ECG) without clinically relevant abnormalities at screening.
* Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
* Ability to communicate well with the investigator and to understand and comply with the requirements of the study.

Exclusion Criteria:

* Known hypersensitivity to any excipients of the drug formulations.
* Treatment with another investigational drug within 30 days prior to screening.
* History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
* Positive results from urine drug screen at screening.
* Excessive caffeine consumption, defined as \>800 mg per day at screening\*.
* African or Hispanic ethnicity.
* History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity.
* Smoking within the last 3 months prior to screening.
* Previous treatment with any prescribed or OTC medications (including herbal medicines such as St John's Wort) within 2 weeks prior to the intended start of study.
* Loss of 250 ml or more of blood within 3 months prior to screening.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
* Legal incapacity or limited legal capacity at screening.

Primary outcomes:
measure: Area under the plasma concentration versus time curve from timepoint 0 to 24 h (AUC24h) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
Secondary outcomes:
measure: Area under the plasma concentration versus time curve from timepoint 0 to infinity (AUC0-inf) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Plasma Concentration (Cmax) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Time (Tmax) of the "Basel Cocktail" in plasma after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Plasma Halflife (t1/2) in the elimination phase of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Area under the concentration in oral fluid versus time curve from timepoint 0 to 24 h (AUC24h) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Area under the concentration in oral fluid versus time curve from timepoint 0 to infinity (AUC0-inf) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Concentration (Cmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Time (Tmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Halflife (t1/2) in the elimination phase of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Area under the concentration in dried blood spots versus time curve from timepoint 0 to 24 h (AUC24h) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Area under the concentration in dried blood spots versus time curve from timepoint 0 to infinity (AUC0-inf) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Concentration (Cmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Peak Time (Tmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
measure: Halflife (t1/2) in the elimination phase of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Phase I Research Unit, University Hospital
Study officials:
affiliation: University Hospital, Basel, Switzerland
name: Manuel Haschke, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Derungs A, Donzelli M, Berger B, Noppen C, Krahenbuhl S, Haschke M. Effects of Cytochrome P450 Inhibition and Induction on the Phenotyping Metrics of the Basel Cocktail: A Randomized Crossover Study. Clin Pharmacokinet. 2016 Jan;55(1):79-91. doi: 10.1007/s40262-015-0294-y.