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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier:
NCT01386593
First received: June 29, 2011
Last updated: March 5, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Metabolic Detoxication, Phase I
Drug: Basel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine)
Drug: "Basel" Cocktail
Drug: Basel cocktail + Rifampicin
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by University Hospital, Basel, Switzerland:

Primary Outcome Measures:
  • 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. [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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. [ Designated as safety issue: No ]
  • Peak Plasma Concentration (Cmax) of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • Peak Time (Tmax) of the "Basel Cocktail" in plasma after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • Plasma Halflife (t1/2) in the elimination phase of the "Basel Cocktail" after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
  • Peak Concentration (Cmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • Peak Time (Tmax) of the "Basel Cocktail" in oral fluid after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]
  • Peak Concentration (Cmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • Peak Time (Tmax) of the "Basel Cocktail" in dried blood spots after inhibition with ciprofloxacin, fluconazole and paroxetine and after induction with rifampicin. [ Designated as safety issue: No ]
  • 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. [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: May 2011
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
(A) Baseline Drug: "Basel" Cocktail
(B) Inhibition Drug: Basel cocktail+(Fluconazole, Ciprofloxacin, Paroxetine)
(C) Induction Drug: Basel cocktail + Rifampicin

  Eligibility

Ages Eligible for Study:   18 Years to 35 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01386593

Locations
Switzerland
Phase I Research Unit, University Hospital
Basel, Switzerland
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Principal Investigator: Manuel Haschke, MD University Hospital, Basel, Switzerland
  More Information

No publications provided

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT01386593     History of Changes
Other Study ID Numbers: EKBB-89/11, 2011 DR 1074
Study First Received: June 29, 2011
Last Updated: March 5, 2012
Health Authority: Switzerland: Swissmedic

Keywords provided by University Hospital, Basel, Switzerland:
Cytochrome
Phenotyping
Pharmacokinetics

Additional relevant MeSH terms:
Ciprofloxacin
Rifampin
Fluconazole
Paroxetine
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Infective Agents
Therapeutic Uses
Antifungal Agents
14-alpha Demethylase Inhibitors
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Leprostatic Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on April 22, 2014