Pharmacokinetic Study to Characterize Phenotyping Metrics of the "Basel" Cocktail After CYP Induction or Inhibition

Condition(s) targeted: Metabolic Detoxification, Phase I

Intervention: Basel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine) (Drug); "Basel" Cocktail (Drug); Basel cocktail + Rifampicin (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: University Hospital, Basel, Switzerland

Official(s) and/or principal investigator(s):
Manuel Haschke, MD, Principal Investigator, Affiliation: University Hospital, Basel, Switzerland

Overall contact:
Manuel Haschke, MD, Phone: +41 61 328 68 66, Email: mhaschke@uhbs.ch

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.

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 design: Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label

Primary outcome: 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 outcome:

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.

Peak Plasma Concentration (Cmax) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

Peak Time (Tmax) of the "Basel Cocktail" in plasma after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

Plasma Halflife (t1/2) in the elimination phase of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

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.

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.

Peak Concentration (Cmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

Peak Time (Tmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

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.

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.

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.

Peak Concentration (Cmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

Peak Time (Tmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin.

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.

Minimum age: 18 Years. Maximum age: 35 Years. Gender(s): Male.

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.

Manuel Haschke, MD, Phone: +41 61 328 68 66, Email: mhaschke@uhbs.ch

Phase I Research Unit, University Hospital, Basel, Switzerland; Recruiting
Manuel Haschke, MD, Principal Investigator

Starting date: May 2011
Last updated: July 4, 2011