<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/NCT02983890</url>
  </required_header>
  <id_info>
    <org_study_id>AKF-388</org_study_id>
    <nct_id>NCT02983890</nct_id>
  </id_info>
  <brief_title>Dicloxacillin: Clinical Relevance of Drug-drug Interactions by Induction of Drug Metabolism.</brief_title>
  <official_title>Dicloxacillin: Clinical Relevance of Drug-drug Interactions by Induction of Drug Metabolizing Enzymes.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Per Damkier</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Odense University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This trial is conducted as a cocktail-study namely an open-label, randomized, two-sequence,&#xD;
      two-period crossover, cocktail study where a combination of cocktail-drugs is used to&#xD;
      illustrate whether or not, or to what degree dicloxacillin affects the level of activity of&#xD;
      the 5 most important CYP enzymes and therefore plays a potentially decisive role in serious&#xD;
      drug-drug interactions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Given knowledge explains dicloxacillin and the drug warfarin to be a potential dangerous drug&#xD;
      drug interaction because the effects of warfarin is downregulated to a degree as to where it&#xD;
      might cause patients to have thrombotic events.&#xD;
&#xD;
      A potential explanation to this is namely dicloxacillin increases the activity of certain&#xD;
      drug metabolising enzymes metabolising warfaring which in turn decreases the concentration of&#xD;
      the drug in the blood and the therapeutic effect.&#xD;
&#xD;
      Cocktail study is the golden standard to investigate as to whether there is changes is P450&#xD;
      enzymes as a result of drug-drug interactions.&#xD;
&#xD;
      The cocktail consists of Midazolam, omeprazole, tolbutamide, caffein and dextromethorphan&#xD;
      which is well known markers for these enzymes. These markers are safe, have specific (enzyme)&#xD;
      metabolism and has been used in several studies with no Serious Adverse reactions reported.&#xD;
&#xD;
      By measuring the Concentration of the drug and its metabolites in plasma / Urine before and&#xD;
      after treatment with dicloxacillin we will estimate AUC (area under the curve) and test our&#xD;
      hypothesis/primary end point of whether there is change in AUC for Tolbutamide (CYP2C9)&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 6, 2016</start_date>
  <completion_date type="Actual">October 1, 2017</completion_date>
  <primary_completion_date type="Actual">April 5, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment</measure>
    <time_frame>Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.</time_frame>
    <description>AUC measurements giving an estimate of activity og the relevant enzymes.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>*AUC(area under the curve) for midazolam (CYP3A4) and dextromethorphan (CYP1A2) omeprazole (CYP2C19) and caffein (CYP1A2)</measure>
    <time_frame>Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T(max)</measure>
    <time_frame>Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.</time_frame>
    <description>The amount of time that the drug is present at the maximum concentration in serum.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>C(max) (peak plasma concentration)</measure>
    <time_frame>Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.</time_frame>
    <description>The peak serum concentration of a therapeutic drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance</measure>
    <time_frame>Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.</time_frame>
    <description>The volume of plasma from which the drug is completely removed per unit time. Reflects rate of drug elimination divided by plasma concentration.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Arm of study1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dicloxacillin tablets.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm of study 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>No treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dicloxacillin</intervention_name>
    <description>Tablets containing dicloxacillin are taken 500mg 2x 3 times per day, for 10 days. Followed by test-day nr 1 at day 11.&#xD;
Both arms receives both treatments, randomly assigned</description>
    <arm_group_label>Arm of study1</arm_group_label>
    <other_name>antibiotics</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>No drug are taken for 10 days. Non-blinded. Followed by test-day nr 1 at day 11.&#xD;
Both arms receives both treatments, randomly assigned</description>
    <arm_group_label>Arm of study 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Are you in a general healthy condition?; questions asked; Are you healthy in general?&#xD;
             2; Do you have any chronic diseases? 3; Are you taking any medications regularly? 4,&#xD;
             Are you taking any medications periodically . 5; Are you taking nutrition supplements,&#xD;
             &quot;nature-medicine&quot; or over-the-counter drugs&#xD;
&#xD;
          -  BMI; range; 18,5-29,9 kg/m2&#xD;
&#xD;
          -  eGFR(estimated glomerular filtration rate), ALAT(alanine aminotransferase), bilirubin,&#xD;
             hæmoglobin og HbA1c, should be within normal limits or without clinically&#xD;
             significantly deviation from these.&#xD;
&#xD;
          -  Non-Smoker&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to applied medications. Known allergy to penicillin or type&#xD;
             1-reaction to cefalosporins.&#xD;
&#xD;
          -  Known allergy to sulfonamides&#xD;
&#xD;
          -  Clinically relevant intake of receipt-required medication, over-the-counter medication&#xD;
             or nutritional supplements.&#xD;
&#xD;
          -  Chronic or daily intake of alcohol.&#xD;
&#xD;
          -  Participation in other Intervention-studies&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Per Damkier, Ph.d.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Assosiated to department of biochemistry and pharmacology at University of southern denmark, Odense</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Klinisk Biokemisk Farmakologi syddansk universitet</name>
      <address>
        <city>Odense</city>
        <state>Funen</state>
        <zip>5000</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>August 21, 2018</last_update_submitted>
  <last_update_submitted_qc>August 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Odense University Hospital</investigator_affiliation>
    <investigator_full_name>Per Damkier</investigator_full_name>
    <investigator_title>Professor, head consultant, MD, ph.d.</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anti-Bacterial Agents</mesh_term>
    <mesh_term>Dicloxacillin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02983890
org study id: AKF-388
nct id: NCT02983890
lead sponsor: 
has dmc: Yes
This trial is conducted as a cocktail-study namely an open-label, randomized, two-sequence,
      two-period crossover, cocktail study where a combination of cocktail-drugs is used to
      illustrate whether or not, or to what degree dicloxacillin affects the level of activity of
      the 5 most important CYP enzymes and therefore plays a potentially decisive role in serious
      drug-drug interactions.
Given knowledge explains dicloxacillin and the drug warfarin to be a potential dangerous drug
      drug interaction because the effects of warfarin is downregulated to a degree as to where it
      might cause patients to have thrombotic events.

      A potential explanation to this is namely dicloxacillin increases the activity of certain
      drug metabolising enzymes metabolising warfaring which in turn decreases the concentration of
      the drug in the blood and the therapeutic effect.

      Cocktail study is the golden standard to investigate as to whether there is changes is P450
      enzymes as a result of drug-drug interactions.

      The cocktail consists of Midazolam, omeprazole, tolbutamide, caffein and dextromethorphan
      which is well known markers for these enzymes. These markers are safe, have specific (enzyme)
      metabolism and has been used in several studies with no Serious Adverse reactions reported.

      By measuring the Concentration of the drug and its metabolites in plasma / Urine before and
      after treatment with dicloxacillin we will estimate AUC (area under the curve) and test our
      hypothesis/primary end point of whether there is change in AUC for Tolbutamide (CYP2C9)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC(area under the curve) for tolbutamid (CYP2C9), as a result of dicloxacillin-treatment
time frame: Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
description: AUC measurements giving an estimate of activity og the relevant enzymes.
measure: *AUC(area under the curve) for midazolam (CYP3A4) and dextromethorphan (CYP1A2) omeprazole (CYP2C19) and caffein (CYP1A2)
time frame: Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
measure: T(max)
time frame: Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
description: The amount of time that the drug is present at the maximum concentration in serum.
measure: C(max) (peak plasma concentration)
time frame: Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
description: The peak serum concentration of a therapeutic drug.
measure: Clearance
time frame: Pharmacological outcome measures at t=0 predose and postdose; 0.5,1,2,3,4,6,8,10,12,24.
description: The volume of plasma from which the drug is completely removed per unit time. Reflects rate of drug elimination divided by plasma concentration.
arm group label: Arm of study1
arm group type: Active Comparator
description: Dicloxacillin tablets.
arm group label: Arm of study 2
arm group type: Placebo Comparator
description: No treatment
intervention type: Drug
intervention name: Dicloxacillin
description: Tablets containing dicloxacillin are taken 500mg 2x 3 times per day, for 10 days. Followed by test-day nr 1 at day 11.
Both arms receives both treatments, randomly assigned
arm group label: Arm of study1
other name: antibiotics
intervention type: Drug
intervention name: Placebos
description: No drug are taken for 10 days. Non-blinded. Followed by test-day nr 1 at day 11.
Both arms receives both treatments, randomly assigned
arm group label: Arm of study 2
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Per Damkier, Ph.d.
role: Principal Investigator
affiliation: Assosiated to department of biochemistry and pharmacology at University of southern denmark, Odense
facility: 
country: Denmark
responsible party type: Sponsor-Investigator
investigator affiliation: Odense University Hospital
investigator full name: Per Damkier
investigator title: Professor, head consultant, MD, ph.d.
mesh term: Anti-Bacterial Agents
mesh term: Dicloxacillin
sharing ipd: No