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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 July 28, 2014