<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/NCT04436562</url>
  </required_header>
  <id_info>
    <org_study_id>SPI-POZ-105</org_study_id>
    <nct_id>NCT04436562</nct_id>
  </id_info>
  <brief_title>Study of the Absorption, Metabolism, and Excretion Following a Single Dose of [14C]-Poziotinib in Healthy Male Subjects</brief_title>
  <official_title>Phase 1 Open-label Study of the Absorption, Metabolism, and Excretion of Poziotinib Following a Single Oral Dose of [14C]-Poziotinib in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spectrum Pharmaceuticals, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spectrum Pharmaceuticals, Inc</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>
      This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects&#xD;
      to evaluate the Absorption, Metabolism, and Excretion of Poziotinib following a single oral&#xD;
      dose of [14C]-poziotinib to healthy male subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Potential subjects will be screened to assess their eligibility to enter the study within 28&#xD;
      days prior to the dose administration. Subjects will be admitted into the Clinical Research&#xD;
      Unit (CRU) on Day -1. On the morning of Day 1, all subjects will receive a single oral dose&#xD;
      of 8 mg (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib in&#xD;
      the fasted state.&#xD;
&#xD;
      Subjects will be confined to the CRU until at least Day 8.&#xD;
&#xD;
      Subjects will be discharged from the CRU on Day 8 if the following criteria are met:&#xD;
&#xD;
        -  ≥90% mass balance recovery in combined urine and feces, and&#xD;
&#xD;
        -  ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in&#xD;
           2 consecutive 24-hour periods in which fecal and urine samples are obtained.&#xD;
&#xD;
      If these criteria are not met by Day 8, subjects will remain in the CRU until all discharge&#xD;
      criteria are met up to a maximum of Day 15 in order to continue 24-hour blood, urine, and&#xD;
      feces collections, unless otherwise agreed upon by the Sponsor and Investigator.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 29, 2020</start_date>
  <completion_date type="Actual">July 17, 2020</completion_date>
  <primary_completion_date type="Actual">July 17, 2020</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]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Attain Maximum Observed Plasma Concentration (Tmax) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(last) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(inf) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of AUCinf Derived by Extrapolation (%AUCext) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>%AUCext of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Half-Life (t1/2) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2 of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Elimination Rate Constant (λz, or kel) of [14C]-Poziotinib, Metabolites M1 and M2</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>λz, or kel of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Volume of Distribution (VZ/F) During Terminal Phase of [14C]-Poziotinib</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Oral Clearance (CL/F) of [14C]-Poziotinib</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Whole Blood : Plasma Concentration Ratios of Total Radioactivity of [14C]-Poziotinib</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Cumulative Amount Excreted in Urine (Aeu)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Fraction of Dose Excreted in Urine (feu)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Cumulative Amount Excreted in Feces (Aef)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Fraction of Dose Excreted in Feces (fef)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Cumulative Total Amount Excreted (Aetotal)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Radioactivity of Fraction of Dose Excreted in Urine and Feces (fetotal)</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Poziotinib Metabolite Profiling and Identification in Plasma</measure>
    <time_frame>1-15 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Adverse Events (AEs)</measure>
    <time_frame>1-15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Hematology, Clinical Chemistry, Urinalysis Laboratory Abnormalities</measure>
    <time_frame>1-15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with 12-lead electrocardiograms (ECG) Abnormalities</measure>
    <time_frame>1-15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Vital Sign and Physical Examinations Abnormalities</measure>
    <time_frame>1-15 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Poziotinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single oral dose of 8 mg poziotinib as a capsule formulation (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C]-Poziotinib</intervention_name>
    <description>Single oral administration of 8 mg (as the hydrocholoride salt) of [14C]-poziotinib</description>
    <arm_group_label>Poziotinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Body mass index between 18.0 and 32.0 kg/m2, inclusive&#xD;
&#xD;
          -  In good health at Screening and/or at Check-in&#xD;
&#xD;
          -  Subjects must be surgically sterile for at least 90 days, or when sexually active with&#xD;
             female partners of childbearing and non-childbearing potential will be required to use&#xD;
             a male condom with spermicide from CRU Check-in until 90 days after discharge.&#xD;
             Subjects are required to refrain from donation of sperm from CRU Check-in until 90&#xD;
             days after discharge&#xD;
&#xD;
          -  Able to comprehend and willing to sign an ICF and to abide by the study restrictions&#xD;
&#xD;
          -  History of at least 1 bowel movement per day&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Stomach or intestinal surgery or resection that would potentially alter absorption&#xD;
             and/or excretion of orally administered drugs&#xD;
&#xD;
          -  Swallowing difficulties or ongoing diarrhea of any etiology&#xD;
&#xD;
          -  Participation in a clinical study involving an investigational drug in the past 30&#xD;
             days prior to dosing&#xD;
&#xD;
          -  Use or intend to use any medications/products known to alter drug absorption,&#xD;
             metabolism, or elimination processes, including St. John's wort, within 30 days prior&#xD;
             to Check-in&#xD;
&#xD;
          -  Use or intend to use any prescription medications/products within 14 days prior to&#xD;
             Check-in&#xD;
&#xD;
          -  Use or intend to use slow-release medications/products considered to still be active&#xD;
             within 14 days prior to Check-in&#xD;
&#xD;
          -  Exposure to significant diagnostic or therapeutic radiation or current employment in a&#xD;
             job requiring radiation exposure monitoring within 12 months prior to Check-in&#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>Shanta Chawla, MD</last_name>
    <role>Study Director</role>
    <affiliation>Spectrum Pharmaceuticals, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Clinical Research Unit, Inc.</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>June 11, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>January 14, 2021</last_update_submitted>
  <last_update_submitted_qc>January 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy Volunteers</keyword>
  <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/NCT04436562
org study id: SPI-POZ-105
nct id: NCT04436562
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This will be a Phase 1, open-label, nonrandomized, single-dose study in healthy male subjects
      to evaluate the Absorption, Metabolism, and Excretion of Poziotinib following a single oral
      dose of [14C]-poziotinib to healthy male subjects.
Potential subjects will be screened to assess their eligibility to enter the study within 28
      days prior to the dose administration. Subjects will be admitted into the Clinical Research
      Unit (CRU) on Day -1. On the morning of Day 1, all subjects will receive a single oral dose
      of 8 mg (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib in
      the fasted state.

      Subjects will be confined to the CRU until at least Day 8.

      Subjects will be discharged from the CRU on Day 8 if the following criteria are met:

        -  ≥90% mass balance recovery in combined urine and feces, and

        -  ≤1% of the total radioactive dose is recovered in combined excreta (urine and feces) in
           2 consecutive 24-hour periods in which fecal and urine samples are obtained.

      If these criteria are not met by Day 8, subjects will remain in the CRU until all discharge
      criteria are met up to a maximum of Day 15 in order to continue 24-hour blood, urine, and
      feces collections, unless otherwise agreed upon by the Sponsor and Investigator.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Maximum Observed Plasma Concentration (Cmax) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: Cmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Time to Attain Maximum Observed Plasma Concentration (Tmax) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: Tmax of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC[last]) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: AUC(last) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: AUC(inf) of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Percentage of AUCinf Derived by Extrapolation (%AUCext) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: %AUCext of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Apparent Terminal Elimination Half-Life (t1/2) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: t1/2 of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Elimination Rate Constant (λz, or kel) of [14C]-Poziotinib, Metabolites M1 and M2
time frame: 1-15 days
measure: λz, or kel of Total Radioactivity of [14C]-Poziotinib in Whole Blood and Plasma
time frame: 1-15 days
measure: Apparent Volume of Distribution (VZ/F) During Terminal Phase of [14C]-Poziotinib
time frame: 1-15 days
measure: Apparent Oral Clearance (CL/F) of [14C]-Poziotinib
time frame: 1-15 days
measure: Whole Blood : Plasma Concentration Ratios of Total Radioactivity of [14C]-Poziotinib
time frame: 1-15 days
measure: Total Radioactivity of Cumulative Amount Excreted in Urine (Aeu)
time frame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Urine (feu)
time frame: 1-15 days
measure: Total Radioactivity of Cumulative Amount Excreted in Feces (Aef)
time frame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Feces (fef)
time frame: 1-15 days
measure: Total Radioactivity of Cumulative Total Amount Excreted (Aetotal)
time frame: 1-15 days
measure: Total Radioactivity of Fraction of Dose Excreted in Urine and Feces (fetotal)
time frame: 1-15 days
measure: Poziotinib Metabolite Profiling and Identification in Plasma
time frame: 1-15 days
measure: Number of Participants with Adverse Events (AEs)
time frame: 1-15 days
measure: Number of Participants with Hematology, Clinical Chemistry, Urinalysis Laboratory Abnormalities
time frame: 1-15 days
measure: Number of Participants with 12-lead electrocardiograms (ECG) Abnormalities
time frame: 1-15 days
measure: Number of Participants with Vital Sign and Physical Examinations Abnormalities
time frame: 1-15 days
arm group label: Poziotinib
arm group type: Experimental
description: A single oral dose of 8 mg poziotinib as a capsule formulation (as the hydrochloride salt) containing approximately 100 μCi of [14C]-poziotinib
intervention type: Drug
intervention name: [14C]-Poziotinib
description: Single oral administration of 8 mg (as the hydrocholoride salt) of [14C]-poziotinib
arm group label: Poziotinib
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shanta Chawla, MD
role: Study Director
affiliation: Spectrum Pharmaceuticals, Inc
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No