<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/NCT04410094</url>
  </required_header>
  <id_info>
    <org_study_id>CR108799</org_study_id>
    <secondary_id>73841937NSC1003</secondary_id>
    <nct_id>NCT04410094</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Effects of Itraconazole and Rifampin on Lazertinib in Healthy Adult Participants</brief_title>
  <official_title>A Phase 1 Open-Label, Fixed-Sequence Drug-Drug Interaction Study to Evaluate the Effects of Steady-state Itraconazole and Rifampin on the Single-dose Pharmacokinetics of Lazertinib Tablets in Healthy Adult Participants</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the effects of multiple doses of strong cytochrome&#xD;
      P450 (CYP) 3A4 inhibitor itraconazole and strong CYP3A4 inducer rifampin on the single dose&#xD;
      pharmacokinetics (PK) of lazertinib in healthy adult participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 14, 2020</start_date>
  <completion_date type="Actual">February 2, 2021</completion_date>
  <primary_completion_date type="Actual">December 30, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cohort 1 and 2: Maximum Plasma Concentration (Cmax) of Lazertinib</measure>
    <time_frame>Predose up to 120 hours post dose</time_frame>
    <description>Cmax is defined as maximum plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time 0 to 120 Hours (AUC [0-120h]) of Lazertinib</measure>
    <time_frame>Predose up to 120 hours post dose</time_frame>
    <description>AUC (0-120h) is defined as area under the plasma concentration-time curve from time 0 to 120 hours postdose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Timepoint (AUC [0-last]) of Lazertinib</measure>
    <time_frame>Predose up to 120 hours post dose</time_frame>
    <description>AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to time of last quantifiable timepoint.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-inf]) of Lazertinib</measure>
    <time_frame>Predose up to 120 hours post dose</time_frame>
    <description>AUC (0-inf) is defined as area under the plasma concentration-time curve from time 0 to infinity, calculated as the sum of AUC(0-last)+C(last)/ lambda(z), where C(last) is the last observed measurable (non-below limit of quantification) concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cohort 1 and 2: Percentage of Area Under the Plasma Concentration from time Zero to Infinite time obtained by Extrapolation (%AUC [0-inf],ex) of Lazertinib</measure>
    <time_frame>Predose up to 120 hours post dose</time_frame>
    <description>%AUC (0-inf),ex is defined as percentage of area under the plasma concentration from time zero to infinite time obtained by extrapolation, calculated as (AUC [0-infinity] minus AUC [0-last]/AUC [0-infinity])*100.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cohort 1 and Cohort 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 65 days (Cohort 1) and up to 70 days (Cohort 2)</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Cohort 1: Lazertinib plus Itraconazole</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by itraconazole capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2: Lazertinib plus Rifampin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by rifampin capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lazertinib</intervention_name>
    <description>Lazertinib tablets will be administered orally.</description>
    <arm_group_label>Cohort 1: Lazertinib plus Itraconazole</arm_group_label>
    <arm_group_label>Cohort 2: Lazertinib plus Rifampin</arm_group_label>
    <other_name>JNJ-73841937; YH25448</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>Itraconazole capsules will be administered orally.</description>
    <arm_group_label>Cohort 1: Lazertinib plus Itraconazole</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Rifampin</intervention_name>
    <description>Rifampin capsules will be administered orally.</description>
    <arm_group_label>Cohort 2: Lazertinib plus Rifampin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A woman must not be of childbearing potential and must have a negative serum&#xD;
             beta-human chorionic gonadotropin (Beta HCG) pregnancy test at screening&#xD;
&#xD;
          -  Hormone replacement therapy (if applicable) must have been discontinued at least 28&#xD;
             days prior to the first dose of study drug (Cohort 2 only)&#xD;
&#xD;
          -  Participants must have a body mass index (BMI) between 18.0 and 32.0 kilogram per&#xD;
             meter square (kg/m^2, inclusive (BMI = weight/height^2), and body weight not less than&#xD;
             50 kg at screening&#xD;
&#xD;
          -  Participants must be healthy based on physical examination, medical history, and vital&#xD;
             signs (pulse and body temperature), performed at screening&#xD;
&#xD;
          -  Male participants must agree to use an adequate contraception method&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current clinically significant medical illness that the investigator&#xD;
             considers should exclude the participant or that could interfere with the&#xD;
             interpretation of the study results&#xD;
&#xD;
          -  History of infection suspected or confirmed to be related to Coronavirus disease 2019&#xD;
             (COVID-19) within 4 weeks before intake of study drug&#xD;
&#xD;
          -  Participant has known allergies, hypersensitivity, or intolerance to lazertinib or its&#xD;
             excipients or to itraconazole and rifampin&#xD;
&#xD;
          -  Participant has contraindications to the use itraconazole and rifampin per local&#xD;
             prescribing information&#xD;
&#xD;
          -  Use of any cytochrome P450 (CYP) 3A4 inhibitors or inducers (other than per-protocol&#xD;
             itraconazole/rifampin administration) within 4 weeks before the first dose of the&#xD;
             study drug is scheduled until completion of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 1, 2020</study_first_posted>
  <last_update_submitted>February 25, 2021</last_update_submitted>
  <last_update_submitted_qc>February 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
    <mesh_term>Rifampin</mesh_term>
    <mesh_term>Lazertinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>The data sharing policy of the Janssen Pharmaceutical Companies of Johnson &amp; Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu</ipd_description>
    <ipd_url>https://www.janssen.com/clinical-trials/transparency</ipd_url>
  </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/NCT04410094
org study id: CR108799
secondary id: 73841937NSC1003
nct id: NCT04410094
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to evaluate the effects of multiple doses of strong cytochrome
      P450 (CYP) 3A4 inhibitor itraconazole and strong CYP3A4 inducer rifampin on the single dose
      pharmacokinetics (PK) of lazertinib in healthy adult participants.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Cohort 1 and 2: Maximum Plasma Concentration (Cmax) of Lazertinib
time frame: Predose up to 120 hours post dose
description: Cmax is defined as maximum plasma concentration.
measure: Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time 0 to 120 Hours (AUC [0-120h]) of Lazertinib
time frame: Predose up to 120 hours post dose
description: AUC (0-120h) is defined as area under the plasma concentration-time curve from time 0 to 120 hours postdose.
measure: Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Timepoint (AUC [0-last]) of Lazertinib
time frame: Predose up to 120 hours post dose
description: AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to time of last quantifiable timepoint.
measure: Cohort 1 and 2: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-inf]) of Lazertinib
time frame: Predose up to 120 hours post dose
description: AUC (0-inf) is defined as area under the plasma concentration-time curve from time 0 to infinity, calculated as the sum of AUC(0-last)+C(last)/ lambda(z), where C(last) is the last observed measurable (non-below limit of quantification) concentration.
measure: Cohort 1 and 2: Percentage of Area Under the Plasma Concentration from time Zero to Infinite time obtained by Extrapolation (%AUC [0-inf],ex) of Lazertinib
time frame: Predose up to 120 hours post dose
description: %AUC (0-inf),ex is defined as percentage of area under the plasma concentration from time zero to infinite time obtained by extrapolation, calculated as (AUC [0-infinity] minus AUC [0-last]/AUC [0-infinity])*100.
measure: Cohort 1 and Cohort 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
time frame: Up to 65 days (Cohort 1) and up to 70 days (Cohort 2)
description: An AE is any untoward medical occurrence in a clinical study participant administered a investigational or non investigational medicinal product. An AE does not necessarily have a causal relationship with the treatment.
arm group label: Cohort 1: Lazertinib plus Itraconazole
arm group type: Experimental
description: Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by itraconazole capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
arm group label: Cohort 2: Lazertinib plus Rifampin
arm group type: Experimental
description: Participants will receive a single oral dose of lazertinib tablets in Treatment Period 1 followed by rifampin capsules orally along with a single oral dose of lazertinib tablet in Treatment Period 2.
intervention type: Drug
intervention name: Lazertinib
description: Lazertinib tablets will be administered orally.
arm group label: Cohort 1: Lazertinib plus Itraconazole
arm group label: Cohort 2: Lazertinib plus Rifampin
other name: JNJ-73841937; YH25448
intervention type: Drug
intervention name: Itraconazole
description: Itraconazole capsules will be administered orally.
arm group label: Cohort 1: Lazertinib plus Itraconazole
intervention type: Drug
intervention name: Rifampin
description: Rifampin capsules will be administered orally.
arm group label: Cohort 2: Lazertinib plus Rifampin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: United States
responsible party type: Sponsor
mesh term: Itraconazole
mesh term: Rifampin
mesh term: Lazertinib
sharing ipd: Yes
ipd description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
ipd url: https://www.janssen.com/clinical-trials/transparency