<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01731067</url>
  </required_header>
  <id_info>
    <org_study_id>Coktail DBS</org_study_id>
    <nct_id>NCT01731067</nct_id>
  </id_info>
  <brief_title>Cocktail Approach for Cytochrome P450 and P-glycoprotein Activity Assessment Using Dried Blood Spot</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Jules Desmeules</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Hospital, Geneva</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and&#xD;
      transporters in vivo. It consists of the administration of probe substances metabolised by a&#xD;
      specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the&#xD;
      determination of a metabolic ratio or the evaluation of the plasmatic or urinary&#xD;
      concentrations of the probe substances. The administration of a cocktail containing several&#xD;
      probe substances allows the simultaneous evaluation of the activity of several cytochromes&#xD;
      and P-gp in a single test.&#xD;
&#xD;
      The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs&#xD;
      for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling&#xD;
      and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion,&#xD;
      flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous&#xD;
      phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.&#xD;
&#xD;
      The modulation of the activity of cytochromes or P-gp will be evaluated by the administration&#xD;
      of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic&#xD;
      pathways or the P-gp mediated transport.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">January 2014</completion_date>
  <primary_completion_date type="Actual">May 2013</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer</measure>
    <time_frame>4 singles days spaced out with one week wash-out periods</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>correlation between plasma or urine and capillary concentrations for each probe cocktail drug</measure>
    <time_frame>4 singles days spaced out with one week wash-out periods</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>comparison. between genotype and phenotype for each enzyme</measure>
    <time_frame>one day</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CYP2D6 and P-gp inhibitor</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CYPs and P-gp inducer</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Oral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Probe cocktail alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral intake of the cocktail probe drugs :&#xD;
bupropion 25 mg&#xD;
flurbiprofen 25 mg&#xD;
omeprazole 5 mg&#xD;
dextromethorphan 5 mg&#xD;
midazolam 1 mg&#xD;
fexofenadine 25mg&#xD;
Caffeine (a cup of coffee)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cocktail probe drugs</intervention_name>
    <arm_group_label>CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors</arm_group_label>
    <arm_group_label>CYP2D6 and P-gp inhibitor</arm_group_label>
    <arm_group_label>CYPs and P-gp inducer</arm_group_label>
    <arm_group_label>Probe cocktail alone</arm_group_label>
    <other_name>Oral intake of the cocktail probe drugs :</other_name>
    <other_name>bupropion 25 mg</other_name>
    <other_name>flurbiprofen 25 mg</other_name>
    <other_name>omeprazole 5 mg</other_name>
    <other_name>dextromethorphan 5 mg</other_name>
    <other_name>midazolam 1 mg</other_name>
    <other_name>fexofenadine 25mg</other_name>
    <other_name>Caffeine (a cup of coffee)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male volunteers aged from 18 to 60 years&#xD;
&#xD;
          -  BMI between 18 and 25&#xD;
&#xD;
          -  Understanding of French language and able to give a written inform consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoker&#xD;
&#xD;
          -  Taking drugs which alter CYPs activity&#xD;
&#xD;
          -  Renal or hepatic impairment&#xD;
&#xD;
          -  Medical history of porphyria&#xD;
&#xD;
          -  Medical history of chronic alcoholism or abuse of psychoactive drugs&#xD;
&#xD;
          -  Liver transplantation&#xD;
&#xD;
          -  Sensitivity to any of the drugs used&#xD;
&#xD;
          -  Wearing contact lenses (risk of coloration with rifampicin)&#xD;
&#xD;
          -  ECG showing long QT interval (&gt;0.46sec)&#xD;
&#xD;
          -  Alteration of hepatic tests&#xD;
&#xD;
          -  Presenting genetic polymorphism of poor CYP 2B6, 2C9, 2C19, 2D6 metabolisers&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jules A Desmeules, Pr</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Hospital, Geneva</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospitals</name>
      <address>
        <city>Geneva 14</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>November 14, 2012</study_first_submitted>
  <study_first_submitted_qc>November 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 21, 2012</study_first_posted>
  <last_update_submitted>September 15, 2014</last_update_submitted>
  <last_update_submitted_qc>September 15, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 16, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University Hospital, Geneva</investigator_affiliation>
    <investigator_full_name>Jules Desmeules</investigator_full_name>
    <investigator_title>Pr</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fexofenadine</mesh_term>
    <mesh_term>Flurbiprofen</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dextromethorphan</mesh_term>
    <mesh_term>Caffeine</mesh_term>
    <mesh_term>Bupropion</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01731067
org study id: Coktail DBS
nct id: NCT01731067
lead sponsor: 
has dmc: No
Phenotyping is an approach largely used for the evaluation of the activity of cytochromes and
      transporters in vivo. It consists of the administration of probe substances metabolised by a
      specific cytochrome or transported by P-glycoprotein (P-gp) for example, followed by the
      determination of a metabolic ratio or the evaluation of the plasmatic or urinary
      concentrations of the probe substances. The administration of a cocktail containing several
      probe substances allows the simultaneous evaluation of the activity of several cytochromes
      and P-gp in a single test.

      The aim of this project is the validation of a phenotyping cocktail of low dose probe drugs
      for the assessment of cytochrome P450 and P-gp activities by simple capillary blood sampling
      and dried blood spot (DBS) analysis. The cocktail consists of caffeine, bupropion,
      flurbiprofen, omeprazole, dextromethorphan, midazolam and fexofenadine for the simultaneous
      phenotyping of CYP1A2, CYP2B6, CYP2C9, CAP2C19, CYP2D6, CYP3A4 and P-gp, respectively.

      The modulation of the activity of cytochromes or P-gp will be evaluated by the administration
      of inhibitors (fluvoxamine, voriconazole, quinidine) or inducer (rifampicin) of the metabolic
      pathways or the P-gp mediated transport.
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Probe cocktail drugs plasma and capillary concentrations in presence/absence of CYP1A2,2B6, 2C9, 2C19, 2D6, 3A4 and P-gp inhibitor or inducer
time frame: 4 singles days spaced out with one week wash-out periods
measure: correlation between plasma or urine and capillary concentrations for each probe cocktail drug
time frame: 4 singles days spaced out with one week wash-out periods
measure: comparison. between genotype and phenotype for each enzyme
time frame: one day
arm group label: CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors
arm group type: Active Comparator
description: Oral intake of fluvoxamine (50 mg per day during 2 days) and voriconazole (400 mg) before oral intake of the cocktail probe drugs
arm group label: CYP2D6 and P-gp inhibitor
arm group type: Active Comparator
description: Oral intake of quinidine (200 mg) before oral intake of the cocktail probe drugs
arm group label: CYPs and P-gp inducer
arm group type: Active Comparator
description: Oral intake of rifampicin (600 mg per day during 7 days) before oral intake of the cocktail probe drugs
arm group label: Probe cocktail alone
arm group type: Experimental
description: Oral intake of the cocktail probe drugs :
bupropion 25 mg
flurbiprofen 25 mg
omeprazole 5 mg
dextromethorphan 5 mg
midazolam 1 mg
fexofenadine 25mg
Caffeine (a cup of coffee)
intervention type: Drug
intervention name: Cocktail probe drugs
arm group label: CYP1A2, 2B6, 2C9, 2C19, 3A4 inhibitors
arm group label: CYP2D6 and P-gp inhibitor
arm group label: CYPs and P-gp inducer
arm group label: Probe cocktail alone
other name: Oral intake of the cocktail probe drugs :
other name: bupropion 25 mg
other name: flurbiprofen 25 mg
other name: omeprazole 5 mg
other name: dextromethorphan 5 mg
other name: midazolam 1 mg
other name: fexofenadine 25mg
other name: Caffeine (a cup of coffee)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jules A Desmeules, Pr
role: Principal Investigator
affiliation: University Hospital, Geneva
facility: 
country: Switzerland
responsible party type: Sponsor-Investigator
investigator affiliation: University Hospital, Geneva
investigator full name: Jules Desmeules
investigator title: Pr
mesh term: Fexofenadine
mesh term: Flurbiprofen
mesh term: Midazolam
mesh term: Dextromethorphan
mesh term: Caffeine
mesh term: Bupropion
mesh term: Omeprazole