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

Study Overview
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Brief Summary
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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
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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

Conditions
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Metabolic Detoxication, Phase I

Intervention / Treatment
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* Drug: Basel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine)
* Drug: Basel Cocktail
* Drug: Basel cocktail + Rifampicin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: (A) Baseline<br> | Drug: Basel Cocktail<br> <br> |
| Other: (B) Inhibition<br> | Drug: Basel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine)<br> <br> |
| Other: (C) Induction<br> | Drug: Basel cocktail + Rifampicin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cytochrome, Phenotyping, Pharmacokinetics