<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/NCT04410081</url>
  </required_header>
  <id_info>
    <org_study_id>CR108791</org_study_id>
    <secondary_id>73841937NSC1004</secondary_id>
    <secondary_id>2020-000646-34</secondary_id>
    <nct_id>NCT04410081</nct_id>
  </id_info>
  <brief_title>A Study of (14C)-JNJ-73841937 (Lazertinib) in Healthy Male Participants</brief_title>
  <official_title>An Open-Label Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-JNJ-73841937 (Lazertinib) After a Single Oral Dose in Healthy Male 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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to characterize the absorption, metabolic pathways of&#xD;
      lazertinib, and the excretion of the parent lazertinib and its metabolites, after a single&#xD;
      oral dose of 14C-lazertinib in healthy adult male participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 14, 2020</start_date>
  <completion_date type="Actual">March 2, 2021</completion_date>
  <primary_completion_date type="Actual">March 2, 2021</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Cmax is defined as maximum observed plasma concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Reach Maximum Observed Plasma Concentration (Tmax) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Tmax is defined time to reach the maximum observed concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUC [0-last]) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to the time of last observed quantifiable concentration.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>AUC (0-infinity) 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 quantifiable concentration, and lambda(z) is elimination rate constant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Half-life (t1/2) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/lambda(z).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Rate Constant (Lambda[z])</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Lambda(z) is defined as apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log transformed concentration vs time data.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Apparent Clearance (CL/F) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Clearance is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose/AUC (0-infinity).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Volume of Distribution (Vdz/F) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Apparent volume of distribution, calculated as dose/(Lambda(z)*AUC (0-infinity).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of Blood to Plasma Total Radioactivity of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Blood to plasma total radioactivity ratio, calculated as blood total radioactivity/plasma total radioactivity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of Total Radioactivity in Plasma</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>The ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of total radioactivity in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of AUC (0-last) of 14C-lazertinib Concentration to AUC (0-last) of Total Radioactivity in Plasma</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>The ratio of AUC (0-last) of 14C-lazertinib to AUC (0-last) of total radioactivity in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of Cmax of 14C-lazertinib to Cmax of Total Radioactivity in Plasma</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>The ratio of Cmax of 14C-lazertinib to Cmax of total radioactivity in plasma will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ratio of 14C-lazertinib Concentration to Total Radioactivity in Plasma</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>The ratio of 14C-lazertinib concentration to total radioactivity in plasma for each sampling time point will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amount of 14C-lazertinib Excreted in Urine (Ae[t1-t2])</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Amount excreted into the urine during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the urinary volume with the urinary concentration for that interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Amount of 14C-lazertinib Excreted in Urine (Ae)</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Cumulative amount excreted into the urine over the entire collection period, calculated as the sum of Ae's across the collection intervals for each participant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of 14C-lazertinib Dose Excreted in Urine (%Ae)</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Cumulative amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae divided by dose)*100.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Renal Clearance (CLr) of 14C-lazertinib</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>The CLr is the renal clearance of the drug, calculated as Ae/AUC(0-infinity).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amount of 14C-lazertinib Excreted in Feces (Fe[t1-t2])</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Amount excreted into the feces during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the feces weight with the feces concentration for that interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Amount of 14C-lazertinib Excreted in Feces (Fe)</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Cumulative amount excreted into the feces over the entire collection period, calculated as the sum of Fe's across the collection intervals for each participant.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of 14C-lazertinib Dose Excreted in Feces (%Fe)</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Cumulative amount excreted into the feces, expressed as a percentage of the administered dose, calculated as (Fe divided by dose)*100.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Recovery of 14C-lazertinib Dose in Feces and Urine</measure>
    <time_frame>Up to 99 days</time_frame>
    <description>Total recovery, calculated as sum of %Ae and %Fe.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability</measure>
    <time_frame>Up to 135 days</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>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>14C-lazertinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single oral dose of 14C-lazertinib on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>14C-lazertinib</intervention_name>
    <description>A single oral dose of 14C-lazertinib will be administered.</description>
    <arm_group_label>14C-lazertinib</arm_group_label>
    <other_name>JNJ-73841937</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be healthy on the basis of medical history performed at screening and physical&#xD;
             examination and vital signs (pulse rate and body temperature) performed at screening&#xD;
             and admission to the study site&#xD;
&#xD;
          -  Participants must be healthy on the basis of clinical laboratory tests performed at&#xD;
             screening. If the results of the serum chemistry or hematology panel are outside the&#xD;
             normal reference ranges, the participant may be included only if the investigator&#xD;
             judges the abnormalities or deviations from normal to be not clinically significant.&#xD;
             This determination must be recorded in the participant's source documents and&#xD;
             initialed by the investigator&#xD;
&#xD;
          -  Body mass index (BMI) between 18.0 and 30.0 kilogram per meter square (kg/m^2,&#xD;
             inclusive (BMI = weight/height^2), and body weight not less than 50 kg at screening&#xD;
&#xD;
          -  Blood pressure at screening and admission to the study site (after the participant&#xD;
             supine for 5 minutes) between 90 and 140 millimeter of Mercury (mmHg) systolic,&#xD;
             inclusive; and no higher than 90 mmHg diastolic at screening&#xD;
&#xD;
          -  A 12-lead electrocardiogram (ECG) consistent with normal cardiac conduction and&#xD;
             function, including: Sinus rhythm, Pulse rate between 45 and 100 beats per minute&#xD;
             (bpm), corrected QT (QTc) interval less than or equal to (&lt;=) 450 millisecond (msec),&#xD;
             QRS interval of less than (&lt;)120 msec, PR interval &lt;210 msec&#xD;
&#xD;
        Exclusion Criteria:&#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 any&#xD;
             of its excipients&#xD;
&#xD;
          -  Participant has a positive test for hepatitis A antibody immunoglobulin M (IgM),&#xD;
             hepatitis B surface antigen (HBsAg), hepatitis B (anti-HBc or anti-HBs), or hepatitis&#xD;
             C (anti-HCV) antibodies positive at screening. Hepatitis B surface antibody positivity&#xD;
             is not exclusionary if participant can provide evidence of Hepatitis B vaccination&#xD;
&#xD;
          -  Participant who plans to father a child while enrolled in the study or within 6 months&#xD;
             after study drug administration&#xD;
&#xD;
          -  Exposure to radiation for professional or medical reasons with the exception of up to&#xD;
             2 standard diagnostic radiographs (example, [dental X-rays, plain chest X-ray]) within&#xD;
             1 year before study drug administration on Study Day 1. Participants cannot have&#xD;
             participated in a radiolabeled drug study within 12 months prior to dosing if the dose&#xD;
             was higher than 0.1 megabecquerel (MBq)&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>PRA Health Sciences Onderzoekscentrum Groningen, locatie Martini</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>March 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>March 25, 2021</last_update_submitted>
  <last_update_submitted_qc>March 25, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 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>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/NCT04410081
org study id: CR108791
secondary id: 73841937NSC1004
secondary id: 2020-000646-34
nct id: NCT04410081
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to characterize the absorption, metabolic pathways of
      lazertinib, and the excretion of the parent lazertinib and its metabolites, after a single
      oral dose of 14C-lazertinib in healthy adult male participants.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax) of 14C-lazertinib
time frame: Up to 99 days
description: Cmax is defined as maximum observed plasma concentration.
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of 14C-lazertinib
time frame: Up to 99 days
description: Tmax is defined time to reach the maximum observed concentration.
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Time of Last Quantifiable Concentration (AUC [0-last]) of 14C-lazertinib
time frame: Up to 99 days
description: AUC (0-last) is defined as area under the plasma concentration-time curve from time 0 to the time of last observed quantifiable concentration.
measure: Area Under the Plasma Concentration-time Curve from Time Zero to Infinity (AUC [0-infinity]) of 14C-lazertinib
time frame: Up to 99 days
description: AUC (0-infinity) 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 quantifiable concentration, and lambda(z) is elimination rate constant.
measure: Elimination Half-life (t1/2) of 14C-lazertinib
time frame: Up to 99 days
description: Elimination half-life associated with the terminal slope lambda(z) of the semilogarithmic drug concentration-time curve, calculated as 0.693/lambda(z).
measure: Apparent Terminal Elimination Rate Constant (Lambda[z])
time frame: Up to 99 days
description: Lambda(z) is defined as apparent terminal elimination rate constant, estimated by linear regression using the terminal log-linear phase of the log transformed concentration vs time data.
measure: Total Apparent Clearance (CL/F) of 14C-lazertinib
time frame: Up to 99 days
description: Clearance is a quantitative measure of the rate at which a drug substance is removed from the body, calculated as dose/AUC (0-infinity).
measure: Apparent Volume of Distribution (Vdz/F) of 14C-lazertinib
time frame: Up to 99 days
description: Apparent volume of distribution, calculated as dose/(Lambda(z)*AUC (0-infinity).
measure: Ratio of Blood to Plasma Total Radioactivity of 14C-lazertinib
time frame: Up to 99 days
description: Blood to plasma total radioactivity ratio, calculated as blood total radioactivity/plasma total radioactivity.
measure: Ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of Total Radioactivity in Plasma
time frame: Up to 99 days
description: The ratio of AUC (0-infinity) of 14C-lazertinib to AUC (0-infinity) of total radioactivity in plasma will be assessed.
measure: Ratio of AUC (0-last) of 14C-lazertinib Concentration to AUC (0-last) of Total Radioactivity in Plasma
time frame: Up to 99 days
description: The ratio of AUC (0-last) of 14C-lazertinib to AUC (0-last) of total radioactivity in plasma will be assessed.
measure: Ratio of Cmax of 14C-lazertinib to Cmax of Total Radioactivity in Plasma
time frame: Up to 99 days
description: The ratio of Cmax of 14C-lazertinib to Cmax of total radioactivity in plasma will be assessed.
measure: Ratio of 14C-lazertinib Concentration to Total Radioactivity in Plasma
time frame: Up to 99 days
description: The ratio of 14C-lazertinib concentration to total radioactivity in plasma for each sampling time point will be assessed.
measure: Amount of 14C-lazertinib Excreted in Urine (Ae[t1-t2])
time frame: Up to 99 days
description: Amount excreted into the urine during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the urinary volume with the urinary concentration for that interval.
measure: Cumulative Amount of 14C-lazertinib Excreted in Urine (Ae)
time frame: Up to 99 days
description: Cumulative amount excreted into the urine over the entire collection period, calculated as the sum of Ae's across the collection intervals for each participant.
measure: Percentage of 14C-lazertinib Dose Excreted in Urine (%Ae)
time frame: Up to 99 days
description: Cumulative amount excreted into the urine, expressed as a percentage of the administered dose, calculated as (Ae divided by dose)*100.
measure: Renal Clearance (CLr) of 14C-lazertinib
time frame: Up to 99 days
description: The CLr is the renal clearance of the drug, calculated as Ae/AUC(0-infinity).
measure: Amount of 14C-lazertinib Excreted in Feces (Fe[t1-t2])
time frame: Up to 99 days
description: Amount excreted into the feces during a collection interval, where t1 and t2 are the start and end times of the collection interval, and calculated by multiplying the feces weight with the feces concentration for that interval.
measure: Cumulative Amount of 14C-lazertinib Excreted in Feces (Fe)
time frame: Up to 99 days
description: Cumulative amount excreted into the feces over the entire collection period, calculated as the sum of Fe's across the collection intervals for each participant.
measure: Percentage of 14C-lazertinib Dose Excreted in Feces (%Fe)
time frame: Up to 99 days
description: Cumulative amount excreted into the feces, expressed as a percentage of the administered dose, calculated as (Fe divided by dose)*100.
measure: Total Recovery of 14C-lazertinib Dose in Feces and Urine
time frame: Up to 99 days
description: Total recovery, calculated as sum of %Ae and %Fe.
measure: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
time frame: Up to 135 days
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: 14C-lazertinib
arm group type: Experimental
description: Participants will receive a single oral dose of 14C-lazertinib on Day 1.
intervention type: Drug
intervention name: 14C-lazertinib
description: A single oral dose of 14C-lazertinib will be administered.
arm group label: 14C-lazertinib
other name: JNJ-73841937
criteria: 
gender: Male
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: Netherlands
responsible party type: Sponsor
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