<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/NCT02994732</url>
  </required_header>
  <id_info>
    <org_study_id>523HV001</org_study_id>
    <nct_id>NCT02994732</nct_id>
  </id_info>
  <brief_title>Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers</brief_title>
  <official_title>A Phase 1 Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-BVD-523 Following Single Oral Dose Administration in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BioMed Valley Discoveries, Inc</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BioMed Valley Discoveries, Inc</source>
  <brief_summary>
    <textblock>
      The primary objective of this study is to characterize the metabolic disposition,&#xD;
      pharmacokinetics (PK), and routes of elimination of [14C]-labeled BVD-523 after&#xD;
      administration of a single, oral dose to healthy male subjects.&#xD;
&#xD;
      The secondary objective of this study is to evaluate the safety and tolerability of a single&#xD;
      oral dose of [14C]-labeled BVD-523 in healthy male subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will be an open-label, absorption, metabolism, and excretion study of&#xD;
      [14C]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male&#xD;
      subjects following a 2-hour fast from food (not including water) that follows breakfast.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">May 15, 2017</completion_date>
  <primary_completion_date type="Actual">February 2017</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax</measure>
    <time_frame>Collected over 5 days</time_frame>
    <description>Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax</measure>
    <time_frame>Collected over 5 days</time_frame>
    <description>peak (maximum) concentration</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2</measure>
    <time_frame>Collected over 15 days</time_frame>
    <description>Elimination half-life</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC</measure>
    <time_frame>Collected over 15 dyas</time_frame>
    <description>Area under Curve (AUC), 0-24 hr</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F</measure>
    <time_frame>Collected over 15 days</time_frame>
    <description>Oral Clearance (CL/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F</measure>
    <time_frame>Collected over 15 days</time_frame>
    <description>Apparent volume of distribution (V/F)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)</measure>
    <time_frame>Collected over 15 days</time_frame>
    <description>Percent of dose excreted in feces</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)</measure>
    <time_frame>Collected over 15 days</time_frame>
    <description>Percent of dose excreted in urine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12</measure>
    <time_frame>Collected in 12 hrs</time_frame>
    <description>AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24</measure>
    <time_frame>Collected in 24 hrs</time_frame>
    <description>AUC from time zero to 24 hrs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment-related Adverse Events</measure>
    <time_frame>27 days</time_frame>
    <description>Any treatment-emergent adverse events related or likely related to study treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>[14C]-BVD-523 600mg single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Open-label, nonrandomized, absorption, metabolism, and excretion study of [14C]-BVD-523 administered as a 600 mg (approximately 200 µCi) oral dose to 6 healthy male subjects following at least an 8-hour fast from food (not including water).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[14C]-BVD-523</intervention_name>
    <description>[14C]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male subjects following a 2-hour fast from food (not including water) that follows breakfast.</description>
    <arm_group_label>[14C]-BVD-523 600mg single dose</arm_group_label>
    <other_name>Ulixertinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males, between 18 and 65 years of age, inclusive, at Screening&#xD;
&#xD;
          -  Have a body mass index range of 18.5 to 32.0 kg/m2, inclusive, at Screening&#xD;
&#xD;
          -  In good health, determined by no clinically significant findings from medical history,&#xD;
             12-lead ECG, and vital signs measurements at Screening or Check-in and PE findings at&#xD;
             Check-in as determined by the Investigator (or designee)&#xD;
&#xD;
          -  Clinical laboratory evaluations (including clinical chemistry panel [fasted at least 8&#xD;
             hours], hematology/complete blood count [CBC], and urinalysis [UA] within the&#xD;
             reference range for the test laboratory at Screening and Check-in, unless deemed not&#xD;
             clinically significant by the Investigator (or designee)&#xD;
&#xD;
          -  Negative test for selected drugs of abuse and cotinine at Screening (does not include&#xD;
             alcohol) and at Check-in (does include alcohol)&#xD;
&#xD;
          -  Negative hepatitis panel (including hepatitis B surface antigen and hepatitis C virus&#xD;
             antibody) and negative human immunodeficiency virus (HIV) antibody screens at&#xD;
             Screening&#xD;
&#xD;
          -  Males will be surgically sterile for at least 90 days (confirmed by documented&#xD;
             azoospermia) or, when sexually-active with female partners of child-bearing potential,&#xD;
             will agree to use contraception as detailed in Section 6.3.3 from Check-in until 90&#xD;
             days following Discharge&#xD;
&#xD;
          -  Males must be willing to refrain from sperm donation from Check-in to 90 days from day&#xD;
             of dosing&#xD;
&#xD;
          -  Able to comprehend and willing to sign an ICF&#xD;
&#xD;
          -  A minimum of 1 bowel movement per day.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant history or clinical manifestation of any metabolic, allergic, infectious,&#xD;
             dermatological, hepatic, renal, hematological, pulmonary, cardiovascular,&#xD;
             gastrointestinal, neurological, or psychiatric disorder (as determined by the&#xD;
             Investigator [or designee]) prior to Check-in&#xD;
&#xD;
          -  History of significant hypersensitivity, intolerance, or allergy to any drug compound,&#xD;
             food, or other substance, unless approved by the Investigator (or designee) prior to&#xD;
             Check-in&#xD;
&#xD;
          -  History of stomach or intestinal surgery or resection that could alter absorption or&#xD;
             excretion of orally administered drugs prior to Check-in except appendectomy, and&#xD;
             hernia repair will be allowed if it was not associated with;&#xD;
&#xD;
          -  History of Gilbert's Syndrome&#xD;
&#xD;
          -  History or presence of an abnormal ECG that, in the Investigator's (or designee's)&#xD;
             opinion, is clinically significant&#xD;
&#xD;
          -  History of alcoholism or drug addiction within 1 year prior to Check-in&#xD;
&#xD;
          -  History of nicotine use within 6 months prior to Check-in or positive cotinine at&#xD;
             Screening or Check-in&#xD;
&#xD;
          -  Participation in more than 1 other radiolabeled investigational study drug trial&#xD;
             within 12 months prior to Check-in. The previous radiolabeled study drug must have&#xD;
             been received more than 6 months prior to Check-in for this study and the total&#xD;
             exposure from this study and the previous study will be within the recommended levels&#xD;
             considered safe, per United States (US) Title 21 Code of Federal Regulations (CFR)&#xD;
             361.1 (eg, less than 3,000 mrem whole body annual exposure)&#xD;
&#xD;
          -  Exposure to significant radiation (eg, serial x-ray or computed tomography scans,&#xD;
             barium meal, current employment in a job requiring radiation exposure monitoring)&#xD;
             within 12 months prior to Check-in&#xD;
&#xD;
          -  Use of any drugs or substances known to be strong inhibitors or strong inducers of&#xD;
             CYP3A enzyme within 30 days prior to study drug administration, unless otherwise&#xD;
             stated, and throughout the study&#xD;
&#xD;
          -  Participation in any other investigational study drug trial in which receipt of an&#xD;
             investigational study drug occurred within 5 half-lives (if known) or 30 days prior to&#xD;
             Check-in, whichever is longer&#xD;
&#xD;
          -  Use of any prescription medications/products within 14 days prior to Check-in, unless&#xD;
             deemed acceptable by the Investigator (or designee)&#xD;
&#xD;
          -  Use of any over-the-counter, nonprescription preparations (including vitamins,&#xD;
             minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days prior&#xD;
             to Check-in, unless deemed acceptable by the Investigator (or designee)&#xD;
&#xD;
          -  Poor peripheral venous access prior to Check-in&#xD;
&#xD;
          -  Donation of whole blood from 56 days prior to Screening through Discharge, inclusive,&#xD;
             or of plasma from 30 days prior to Screening through Discharge, inclusive&#xD;
&#xD;
          -  Receipt of blood products within 2 months prior to Check-in&#xD;
&#xD;
          -  Any acute or chronic condition that, in the opinion of the Investigator (or designee),&#xD;
             would limit the subject's ability to complete or participate in this clinical study&#xD;
&#xD;
          -  Any other unspecified reason that, in the opinion of the Investigator (or designee) or&#xD;
             Sponsor, make the subject unsuitable for enrollment&#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>Irene Mirkin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Covance</affiliation>
  </overall_official>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>November 14, 2016</study_first_submitted>
  <study_first_submitted_qc>December 13, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 16, 2016</study_first_posted>
  <results_first_submitted>April 24, 2018</results_first_submitted>
  <results_first_submitted_qc>March 14, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 17, 2019</results_first_posted>
  <last_update_submitted>March 14, 2019</last_update_submitted>
  <last_update_submitted_qc>March 14, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 7, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT02994732/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 29, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/32/NCT02994732/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Experimental [14C] - BVD-523 600mg Single Dose</title>
          <description>Subjects received a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that followed breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6">All subjects entered clinic on January 11, 2017</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6">All subjects were discharged from the clinic by Jan 24, 2017</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Single Arm Study</title>
          <description>Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="39.0" spread="16.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.9" spread="2.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax</title>
        <description>Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose.</description>
        <time_frame>Collected over 5 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax</title>
          <description>Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose.</description>
          <population>All enrolled subjects</population>
          <units>hr</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.57" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax</title>
        <description>peak (maximum) concentration</description>
        <time_frame>Collected over 5 days</time_frame>
        <population>All 6 subjects enrolled</population>
        <group_list>
          <group group_id="O1">
            <title>Single Arm Study</title>
            <description>Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax</title>
          <description>peak (maximum) concentration</description>
          <population>All 6 subjects enrolled</population>
          <units>ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1110" spread="619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2</title>
        <description>Elimination half-life</description>
        <time_frame>Collected over 15 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2</title>
          <description>Elimination half-life</description>
          <population>All enrolled subjects</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.75" spread="3.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC</title>
        <description>Area under Curve (AUC), 0-24 hr</description>
        <time_frame>Collected over 15 dyas</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC</title>
          <description>Area under Curve (AUC), 0-24 hr</description>
          <population>All enrolled subjects</population>
          <units>hr*ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8480" spread="3600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F</title>
        <description>Oral Clearance (CL/F)</description>
        <time_frame>Collected over 15 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F</title>
          <description>Oral Clearance (CL/F)</description>
          <population>All enrolled subjects</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73" spread="35.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F</title>
        <description>Apparent volume of distribution (V/F)</description>
        <time_frame>Collected over 15 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F</title>
          <description>Apparent volume of distribution (V/F)</description>
          <population>All enrolled subjects</population>
          <units>L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="899" spread="463"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)</title>
        <description>Percent of dose excreted in feces</description>
        <time_frame>Collected over 15 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)</title>
          <description>Percent of dose excreted in feces</description>
          <population>All enrolled subjects</population>
          <units>%of radioactive dose of [14C-BVD523</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="82" spread="4.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)</title>
        <description>Percent of dose excreted in urine</description>
        <time_frame>Collected over 15 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)</title>
          <description>Percent of dose excreted in urine</description>
          <population>All enrolled subjects</population>
          <units>% of radioactive dose of [14C-BVD523</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.8" spread="4.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12</title>
        <description>AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation</description>
        <time_frame>Collected in 12 hrs</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12</title>
          <description>AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation</description>
          <population>All enrolled subjects</population>
          <units>hr*ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.464" spread="0.0354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24</title>
        <description>AUC from time zero to 24 hrs</description>
        <time_frame>Collected in 24 hrs</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Experimental [14C] -BVD-523 600mg Single Dose</title>
            <description>Subjects will receive a single oral 600-mg (4 ×150-mg capsules) dose of BVD-523 containing approximately 200 µCi of [14C] labeled BVD-523 following a 2-hour fast that follows breakfast. Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24</title>
          <description>AUC from time zero to 24 hrs</description>
          <population>All enrolled subjects</population>
          <units>hr*ng/ml</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.409" spread="0.0297"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment-related Adverse Events</title>
        <description>Any treatment-emergent adverse events related or likely related to study treatment</description>
        <time_frame>27 days</time_frame>
        <population>All enrolled subjects</population>
        <group_list>
          <group group_id="O1">
            <title>Single Arm Study</title>
            <description>Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment-related Adverse Events</title>
          <description>Any treatment-emergent adverse events related or likely related to study treatment</description>
          <population>All enrolled subjects</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>27 days</time_frame>
      <desc>Adverse event definitions; assignment of severity, causality, action taken, and outcome; and procedures for reporting serious AEs (SAEs) are detailed in Appendix C of the protocol. None of the definitions differ from the clinicaltrials.gov definitions.</desc>
      <group_list>
        <group group_id="E1">
          <title>Single Arm Study</title>
          <description>Six subjects were enrolled in, dosed, and completed study. All six subjects were male, 4 subjects were white and 2 subjects were black or African American.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Associate Director of Translational Sciences</name_or_title>
      <organization>Biomed Valley Discoveries</organization>
      <phone>636-887-6429</phone>
      <email>Dknoerzer@biomed-valley.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02994732
org study id: 523HV001
nct id: NCT02994732
lead sponsor: 
The primary objective of this study is to characterize the metabolic disposition,
      pharmacokinetics (PK), and routes of elimination of [14C]-labeled BVD-523 after
      administration of a single, oral dose to healthy male subjects.

      The secondary objective of this study is to evaluate the safety and tolerability of a single
      oral dose of [14C]-labeled BVD-523 in healthy male subjects.
This study will be an open-label, absorption, metabolism, and excretion study of
      [14C]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male
      subjects following a 2-hour fast from food (not including water) that follows breakfast.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Tmax
time frame: Collected over 5 days
description: Time to peak concentration (Tmax), PK blood samples were taken at the following time points 0 (predose), 30 min, 1, 2, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144 and 168 hours post dose.
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) Cmax
time frame: Collected over 5 days
description: peak (maximum) concentration
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) t1/2
time frame: Collected over 15 days
description: Elimination half-life
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) AUC
time frame: Collected over 15 dyas
description: Area under Curve (AUC), 0-24 hr
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) CL/F
time frame: Collected over 15 days
description: Oral Clearance (CL/F)
measure: Pharmacokinetics of 14C-labeled BVD-523(Radioactivity in Whole Blood and Plasma) V/F
time frame: Collected over 15 days
description: Apparent volume of distribution (V/F)
measure: Excretion Rate of 14C-labeled BVD-523(Radioactivity in Feces)
time frame: Collected over 15 days
description: Percent of dose excreted in feces
measure: Excretion Rate of 14C-labeled BVD-523(Radioactivity in Urine)
time frame: Collected over 15 days
description: Percent of dose excreted in urine
measure: Cumulative Whole Blood: Plasma Ratio Calculated for AUC0-12
time frame: Collected in 12 hrs
description: AUC from time zero to the 12 hr time point with concentration above the lower limit of quantitation
measure: Cumulative Whole Blood: Plasma Ratio Calculated for AUC 0-24
time frame: Collected in 24 hrs
description: AUC from time zero to 24 hrs
measure: Treatment-related Adverse Events
time frame: 27 days
description: Any treatment-emergent adverse events related or likely related to study treatment
arm group label: [14C]-BVD-523 600mg single dose
arm group type: Experimental
description: Open-label, nonrandomized, absorption, metabolism, and excretion study of [14C]-BVD-523 administered as a 600 mg (approximately 200 µCi) oral dose to 6 healthy male subjects following at least an 8-hour fast from food (not including water).
intervention type: Drug
intervention name: [14C]-BVD-523
description: [14C]-BVD-523 administered as a 600-mg (approximately 200 µCi) oral dose to 6 healthy male subjects following a 2-hour fast from food (not including water) that follows breakfast.
arm group label: [14C]-BVD-523 600mg single dose
other name: Ulixertinib
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Irene Mirkin, MD
role: Principal Investigator
affiliation: Covance
responsible party type: Sponsor
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 