<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/NCT02975037</url>
  </required_header>
  <id_info>
    <org_study_id>CYP3A_DDI</org_study_id>
    <nct_id>NCT02975037</nct_id>
  </id_info>
  <brief_title>Evaluation of Metabolic Markers for the Prediction of DDI of Various CYP3A Substrates and Inhibitors</brief_title>
  <official_title>Evaluation and Validation of Metabolic Markers for the Prediction of Drug-drug Interaction of Various CYP3A4 Substrates and Inhibitors in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Evaluation and validation of metabolic markers for the prediction of drug-drug interaction of&#xD;
      various CYP3A4 substrates (sildenafil) and inhibitors (erythromycin/itraconazole) in healthy&#xD;
      male subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects suitable for this study will be admitted to the Clinical Trials Center, Seoul&#xD;
      National University Hospital on the day before dosing, and they will be overnight-fasted from&#xD;
      9P of Day -1. Urine collection is scheduled from 12 hours before sildenafil administration to&#xD;
      12 hours after administration. Subjects will be administered sildenafil (oral) around at 9A&#xD;
      of Day 1. Subjects will perform scheduled procedures including clinical laboratory tests,&#xD;
      electrocardiograms and blood samplings for pharmacokinetic, pharmacometabolomic and mRNA&#xD;
      assessment.&#xD;
&#xD;
      Subjects will be administered either erythromycin or itraconazole (oral) around at 9A on Day&#xD;
      3 and 9A/9P on Day 4. Urine collection is scheduled from 0 hour to 12 hours after Day 3&#xD;
      erythromycin or itraconazole administration. Subjects will perform scheduled procedures&#xD;
      including clinical laboratory tests, electrocardiograms and blood samplings for&#xD;
      pharmacokinetic, pharmacometabolomic and mRNA assessment.&#xD;
&#xD;
      On Day 5, sildenafil will be administered with erythromycin or itraconazole around at 9A.&#xD;
      Urine collection is scheduled from 12 hours before Day 5 drug administration to 12 hours&#xD;
      after administration. Subjects will perform scheduled procedures. After subjects perform&#xD;
      scheduled procedure, the study will be discharged (around 9A of Day 6).&#xD;
&#xD;
      Study participation was terminated on post-study visit (Day 12-14).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 6, 2017</start_date>
  <completion_date type="Actual">June 23, 2017</completion_date>
  <primary_completion_date type="Actual">March 4, 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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Quantification of endogenous metabolites (plasma)</measure>
    <time_frame>day 1 0h, day 3 0h, day 5 0h</time_frame>
    <description>Metabolomic profiles to predict CYP3A activity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quantification of endogenous metabolites (urine)</measure>
    <time_frame>day -1 12h~day 1 0h, day 1 0h~12h, day 3 0h~12h, day 4 12h~ day 5 0h, day 5 0h~12h</time_frame>
    <description>Metabolomic profiles to predict CYP3A activity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax)</measure>
    <time_frame>day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h</time_frame>
    <description>Pharmacokinetics of CYP3A substrate and inhibitors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h</time_frame>
    <description>Pharmacokinetics of CYP3A substrate and inhibitors</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Quantification of mRNA (whole blood)</measure>
    <time_frame>day -1 12h, day 1 0, 12h, day 3 0, 12h, day 4 12h, day 5 0, 12h</time_frame>
    <description>Quantification of mRNA for CYP3A activity</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>sildenafil+clarithromycin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sildenafil 25 mg PO (single dose); Clarithromycin 250 mg PO (3 doses); Sildenafil 25 mg PO + Clarithromycin 250 mg PO (single dose)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sildenafil+itraconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sildenafil 25 mg PO (single dose); Itraconazole 100 mg PO (3 doses); Sildenafil 25 mg PO + Itraconazole 100 mg PO (single dose)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sildenafil</intervention_name>
    <description>sildenafil 25 mg PO</description>
    <arm_group_label>sildenafil+clarithromycin</arm_group_label>
    <arm_group_label>sildenafil+itraconazole</arm_group_label>
    <other_name>VIAGRA TAB, Pfizer Pharmaceuticals Korea Limited, Korea</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Clarithromycin</intervention_name>
    <description>clarithromycin 250 mg PO</description>
    <arm_group_label>sildenafil+clarithromycin</arm_group_label>
    <other_name>CLARI TAB, Hanmi Pharm.Co.,Ltd., Korea</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>itraconazole 100 mg PO</description>
    <arm_group_label>sildenafil+itraconazole</arm_group_label>
    <other_name>ITRA TAB, Hanmi Pharm.Co.,Ltd., Korea</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age: Between 19 to 50 years of age, inclusive&#xD;
&#xD;
          -  Weight: within 17-28 of Body Mass Index (BMI)&#xD;
&#xD;
          -  Subject who are reliable and willing to make themselves available during the study&#xD;
             period.&#xD;
&#xD;
          -  Subject who are willing to follow the study protocol, and give their written informed&#xD;
             consent voluntarily.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of hypersensitive reaction to medication (midazolam, itraconazole, rifampicin)&#xD;
&#xD;
          -  History of significant clinical illness needs medical caution, including&#xD;
             cardiovascular, immunologic, hematologic, neuropsychiatric, respiratory,&#xD;
             gastrointestinal, hepatic, or renal disease or other chronic disease&#xD;
&#xD;
          -  History or evidence of drug abuse&#xD;
&#xD;
          -  Use any prescriptive medication, Korean traditional medication not considered&#xD;
             acceptable by the clinical investigator during the last 14 days period before first&#xD;
             dosing, or use any medication not considered acceptable by the clinical investigator&#xD;
             during the last 7 days period before first dosing (if used medication is considered&#xD;
             acceptable by investigator, patients can be included)&#xD;
&#xD;
          -  Participation in clinical trials of any drug within 3 months prior to the&#xD;
             participation of the study&#xD;
&#xD;
          -  Judged to be inappropriate for the study by the investigator&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joo-Youn Cho</last_name>
    <role>Principal Investigator</role>
    <affiliation>Seoul National University Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>November 21, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <last_update_submitted>October 25, 2022</last_update_submitted>
  <last_update_submitted_qc>October 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Joo-Youn Cho</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Clarithromycin</mesh_term>
    <mesh_term>Itraconazole</mesh_term>
    <mesh_term>Sildenafil Citrate</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/NCT02975037
org study id: CYP3A_DDI
nct id: NCT02975037
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Evaluation and validation of metabolic markers for the prediction of drug-drug interaction of
      various CYP3A4 substrates (sildenafil) and inhibitors (erythromycin/itraconazole) in healthy
      male subjects
Subjects suitable for this study will be admitted to the Clinical Trials Center, Seoul
      National University Hospital on the day before dosing, and they will be overnight-fasted from
      9P of Day -1. Urine collection is scheduled from 12 hours before sildenafil administration to
      12 hours after administration. Subjects will be administered sildenafil (oral) around at 9A
      of Day 1. Subjects will perform scheduled procedures including clinical laboratory tests,
      electrocardiograms and blood samplings for pharmacokinetic, pharmacometabolomic and mRNA
      assessment.

      Subjects will be administered either erythromycin or itraconazole (oral) around at 9A on Day
      3 and 9A/9P on Day 4. Urine collection is scheduled from 0 hour to 12 hours after Day 3
      erythromycin or itraconazole administration. Subjects will perform scheduled procedures
      including clinical laboratory tests, electrocardiograms and blood samplings for
      pharmacokinetic, pharmacometabolomic and mRNA assessment.

      On Day 5, sildenafil will be administered with erythromycin or itraconazole around at 9A.
      Urine collection is scheduled from 12 hours before Day 5 drug administration to 12 hours
      after administration. Subjects will perform scheduled procedures. After subjects perform
      scheduled procedure, the study will be discharged (around 9A of Day 6).

      Study participation was terminated on post-study visit (Day 12-14).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Quantification of endogenous metabolites (plasma)
time frame: day 1 0h, day 3 0h, day 5 0h
description: Metabolomic profiles to predict CYP3A activity
measure: Quantification of endogenous metabolites (urine)
time frame: day -1 12h~day 1 0h, day 1 0h~12h, day 3 0h~12h, day 4 12h~ day 5 0h, day 5 0h~12h
description: Metabolomic profiles to predict CYP3A activity
measure: Peak plasma concentration (Cmax)
time frame: day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h
description: Pharmacokinetics of CYP3A substrate and inhibitors
measure: Area under the plasma concentration versus time curve (AUC)
time frame: day 1 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 3 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h; day 5 0h (pre-dose), 10, 20, 30, 45 min, 1, 2, 3, 4, 6, 8, 12, 24h
description: Pharmacokinetics of CYP3A substrate and inhibitors
measure: Quantification of mRNA (whole blood)
time frame: day -1 12h, day 1 0, 12h, day 3 0, 12h, day 4 12h, day 5 0, 12h
description: Quantification of mRNA for CYP3A activity
arm group label: sildenafil+clarithromycin
arm group type: Experimental
description: Sildenafil 25 mg PO (single dose); Clarithromycin 250 mg PO (3 doses); Sildenafil 25 mg PO + Clarithromycin 250 mg PO (single dose)
arm group label: sildenafil+itraconazole
arm group type: Experimental
description: Sildenafil 25 mg PO (single dose); Itraconazole 100 mg PO (3 doses); Sildenafil 25 mg PO + Itraconazole 100 mg PO (single dose)
intervention type: Drug
intervention name: Sildenafil
description: sildenafil 25 mg PO
arm group label: sildenafil+clarithromycin
arm group label: sildenafil+itraconazole
other name: VIAGRA TAB, Pfizer Pharmaceuticals Korea Limited, Korea
intervention type: Drug
intervention name: Clarithromycin
description: clarithromycin 250 mg PO
arm group label: sildenafil+clarithromycin
other name: CLARI TAB, Hanmi Pharm.Co.,Ltd., Korea
intervention type: Drug
intervention name: Itraconazole
description: itraconazole 100 mg PO
arm group label: sildenafil+itraconazole
other name: ITRA TAB, Hanmi Pharm.Co.,Ltd., Korea
criteria: 
gender: Male
minimum age: 19 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Joo-Youn Cho
role: Principal Investigator
affiliation: Seoul National University Hospital
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Joo-Youn Cho
investigator title: Professor
mesh term: Clarithromycin
mesh term: Itraconazole
mesh term: Sildenafil Citrate
sharing ipd: No