<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/NCT04473664</url>
  </required_header>
  <id_info>
    <org_study_id>AC220-A-U105</org_study_id>
    <nct_id>NCT04473664</nct_id>
  </id_info>
  <brief_title>A Study of Quizartinib Pharmacokinetics in Participants With Moderate Hepatic Impairment</brief_title>
  <official_title>An Open-label, Single-dose Study to Assess the Pharmacokinetics, Safety and Tolerability of Quizartinib in Subjects With Moderate Impaired Hepatic Function as Defined by NCI-ODWG Criteria</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Daiichi Sankyo, 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>
      Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting&#xD;
      highly potent and selective but reversible inhibition of Feline McDonough sarcoma (FMS)-like&#xD;
      tyrosine kinase 3 (FLT3). Quizartinib is currently being studied alone or in combination with&#xD;
      other agents as a treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome&#xD;
      (MDS) in adult and pediatric populations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to determine the plasma pharmacokinetics (PK) of&#xD;
      quizartinib and its pharmacologically active metabolite AC886 after a single oral dose of 30&#xD;
      mg in participants with moderate hepatic impairment (HI) (as defined by National Cancer&#xD;
      Institute-Organ Dysfunction Working Group [NCI-ODWG] criteria) compared to the healthy&#xD;
      control participants with normal hepatic function.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 22, 2020</start_date>
  <completion_date type="Actual">July 22, 2021</completion_date>
  <primary_completion_date type="Actual">July 22, 2021</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Terminal Half-Life (t1/2) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Half-Life (t1/2) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. AUClast and AUCinf was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</measure>
    <time_frame>Baseline up to 30 days after last dose, up to 2 months</time_frame>
    <description>A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Hepatic Impairment</condition>
  <condition>Moderate Impaired Hepatic Function</condition>
  <arm_group>
    <arm_group_label>Participants with Moderate Hepatic Impairment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Participants with Normal Hepatic Function</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quizartinib</intervention_name>
    <description>Single oral dose, 30 mg tablet</description>
    <arm_group_label>Control Participants with Normal Hepatic Function</arm_group_label>
    <arm_group_label>Participants with Moderate Hepatic Impairment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female subjects 18 years to 75 years of age (inclusive), with a body mass&#xD;
             index (BMI) of 18 kg/m^2 to 36 kg/m^2 (inclusive)&#xD;
&#xD;
          -  In females, documented surgical sterilization, postmenopausal status for at least 1&#xD;
             year (follicle stimulating hormone [FSH] &gt; 40 mIU/mL serum at Screening), or agreement&#xD;
             to use an approved form of contraception&#xD;
&#xD;
          -  In males, documented surgical sterilization, sexual abstinence, or agreement to use an&#xD;
             approved form of contraception from Screening until 6 months after the dose of&#xD;
             quizartinib&#xD;
&#xD;
          -  In males, agreement to avoid sperm donation for 6 months days after the dose of&#xD;
             quizartinib&#xD;
&#xD;
          -  Participants must agree to refrain from donation of blood from 56 days prior to&#xD;
             Screening, plasma from 2 weeks prior to Screening, and platelets from 6 weeks prior to&#xD;
             Screening.&#xD;
&#xD;
          -  All participants must be willing to refrain from consuming grapefruit/grapefruit&#xD;
             juice, Seville oranges, and pomegranates/pomegranate juice 10 days before the dose of&#xD;
             the study drug is given on Day 1 until end-of-study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any serious and/or unstable pre-existing medical, psychiatric disorder, or other&#xD;
             conditions (including lab abnormality) that could interfere with participant's safety,&#xD;
             obtaining informed consent or compliance to the study procedures&#xD;
&#xD;
          -  Laboratory results (serum chemistry, hematology, and urinalysis) outside the normal&#xD;
             range, if considered clinically significant by the investigator Estimated glomerular&#xD;
             filtration rate (eGFR) &lt; 90 mL/min at screening.&#xD;
&#xD;
          -  Women who are pregnant or breastfeeding&#xD;
&#xD;
          -  Use of any drugs or substances known to be inhibitors or inducers of CYP3A4/5 within&#xD;
             28 days from the first dose or 5 half-lives, if known, of the drugs or substances,&#xD;
             whichever is greater, prior to quizartinib administration and during the study.&#xD;
&#xD;
          -  Receipt of any prescribed or over-the-counter (OTC) systemic, herbal (including St&#xD;
             John's wort), or topical medication within 14 days of quizartinib administration, or&#xD;
             any expectation of requiring use of such medication while participating in the study&#xD;
             is prohibited.&#xD;
&#xD;
          -  A positive drugs of abuse screen from a urine ethanol test (unless the drug is&#xD;
             medically prescribed by a licensed health care provider) or alcohol breath test at&#xD;
             Screening or at Check-in on Day -1 or a participant who will not agree to smoke ≤10&#xD;
             cigarettes or equivalent per day from Screening up to Enrollment, and is unable to be&#xD;
             restricted to ≤5 cigarettes per day and for 6 hours post dose during their period of&#xD;
             residence in the clinical unit&#xD;
&#xD;
          -  Concomitant use of medications known to affect the elimination of serum creatinine&#xD;
             (e.g., trimethoprim or cimetidine) and inhibitors of renal tubular secretion (eg,&#xD;
             probenecid) within 14 days or 5 half-lives, if known, of the drugs, whichever is&#xD;
             greater, prior to quizartinib administration&#xD;
&#xD;
          -  Diagnosis of or suspicion of long QT syndrome (including family history of long QT&#xD;
             syndrome.&#xD;
&#xD;
          -  Use of drugs with a risk of QT interval prolongation or torsade de pointes within 14&#xD;
             days of Day -1 (or 5 drug half-lives, if 5 drug half-lives are expected to exceed 14&#xD;
             days)&#xD;
&#xD;
          -  Consumption of alcohol- and caffeine-containing beverages within 72 hours prior to&#xD;
             check-in and during confinement&#xD;
&#xD;
          -  Positive serology for hepatitis B surface antigen (HBsAg) and HCV (healthy subjects),&#xD;
             hepatitis A virus (HAV) immunoglobulin M, or anti-human immunodeficiency virus (HIV)&#xD;
             Type 1 and Type 2 (all participants)&#xD;
&#xD;
          -  Current enrollment in or have not yet completed at least 30 days or 5 elimination&#xD;
             half-lives, whichever is longer, since receiving an investigational device or product,&#xD;
             or receipt of other investigational agents within 30 days of quizartinib&#xD;
&#xD;
        Additional Exclusion Criteria for Matched Healthy Participants:&#xD;
&#xD;
          -  Any clinically relevant abnormality identified on the physical examination, ECG, vital&#xD;
             signs, or laboratory tests at Screening&#xD;
&#xD;
          -  Liver function (aspartate aminotransferase, alanine aminotransferase, alkaline&#xD;
             phosphatase of liver origin, gamma-glutamyl transferase, and total bilirubin) test&#xD;
             results above the upper limit of normal at Screening and during Enrollment on Day -2&#xD;
             are exclusionary. If transaminase levels are &gt;2 × upper limit of normal (ULN) at&#xD;
             Screening the participant will be excluded and cannot be rescreened&#xD;
&#xD;
        Additional Exclusion Criteria for Participants with Hepatic Impairment:&#xD;
&#xD;
          -  Participants with active stage 3 or stage 4 encephalopathy&#xD;
&#xD;
          -  Fluctuating or rapidly deteriorating hepatic function as indicated by recent history&#xD;
             or worsening of clinical and/or laboratory signs of HI as judged by the investigator&#xD;
&#xD;
          -  Participants with severe ascites and/or need of regular paracentesis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Global Clinical Leader</last_name>
    <role>Study Director</role>
    <affiliation>Daiichi Sankyo, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical Pharmacology of Miami, LLC</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33014-3616</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Pharma</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33147</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Orlando Clinical Research Center</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32809</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <results_first_submitted>March 25, 2022</results_first_submitted>
  <results_first_submitted_qc>September 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 1, 2023</results_first_posted>
  <last_update_submitted>September 20, 2022</last_update_submitted>
  <last_update_submitted_qc>September 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hepatic Impairment</keyword>
  <keyword>Healthy Subjects</keyword>
  <keyword>Drug-drug Interaction</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Quizartinib</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.</ipd_time_frame>
    <ipd_access_criteria>Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.</ipd_access_criteria>
    <ipd_url>https://vivli.org/ourmember/daiichi-sankyo/</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 17, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT04473664/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 12 participants who met all inclusion criteria and no exclusion criteria were enrolled from 22 Sep 2020 to 22 Jul 2021 at 3 clinics in the United States.</recruitment_details>
      <pre_assignment_details>This study included a screening period up to 22 days prior to the enrolment and a 22 day in-clinic period, including screening.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Participants With Moderate Hepatic Impairment</title>
          <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
        </group>
        <group group_id="P2">
          <title>Control Participants With Normal Hepatic Function</title>
          <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</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"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Participants With Moderate Hepatic Impairment</title>
          <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
        </group>
        <group group_id="B2">
          <title>Control Participants With Normal Hepatic Function</title>
          <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="57.0" spread="6.78"/>
                    <measurement group_id="B2" value="55.3" spread="3.88"/>
                    <measurement group_id="B3" value="56.2" spread="5.34"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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 group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86.2" spread="15.8"/>
                    <measurement group_id="O2" value="90.7" spread="17.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean]</param_type>
            <param_value>95.1</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.1</ci_lower_limit>
            <ci_upper_limit>117</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" lower_limit="2.0" upper_limit="4.0"/>
                    <measurement group_id="O2" value="4.0" lower_limit="2.0" upper_limit="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>ng*h/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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUClast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7480" spread="2930"/>
                    <measurement group_id="O2" value="7720" spread="4750"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCinf</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7880" spread="3540"/>
                    <measurement group_id="O2" value="8110" spread="5120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUClast statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean]</param_type>
            <param_value>109</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>59.5</ci_lower_limit>
            <ci_upper_limit>201</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUCinf statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean]</param_type>
            <param_value>109</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>57.9</ci_lower_limit>
            <ci_upper_limit>207</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>L/h</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.0" spread="1.9"/>
                    <measurement group_id="O2" value="5.0" spread="3.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>Liters</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="479" spread="121"/>
                    <measurement group_id="O2" value="577" spread="269"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Terminal Half-Life (t1/2) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-Life (t1/2) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>hours</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93.7" spread="36.0"/>
                    <measurement group_id="O2" value="96.3" spread="34.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.3" spread="12.1"/>
                    <measurement group_id="O2" value="24.7" spread="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical comparison was analyzed for AC886.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>74.4</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>32.0</ci_lower_limit>
            <ci_upper_limit>173</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.00" lower_limit="4.00" upper_limit="48.0"/>
                    <measurement group_id="O2" value="7.00" lower_limit="4.00" upper_limit="72.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.</population>
          <units>ng*h/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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AUClast</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2180" spread="1110"/>
                    <measurement group_id="O2" value="3240" spread="1280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AUCinf</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2610" spread="878"/>
                    <measurement group_id="O2" value="3700" spread="1130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUClast statistical comparison was analyzed for AC886.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>62.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>35.3</ci_lower_limit>
            <ci_upper_limit>111</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUCinf statistical comparison was analyzed for AC886.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>69.9</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>46.8</ci_lower_limit>
            <ci_upper_limit>104</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Half-Life (t1/2) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Half-Life (t1/2) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>hours</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="111.1" spread="48.7"/>
                    <measurement group_id="O2" value="81.4" spread="20.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. AUClast and AUCinf was assessed.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. AUClast and AUCinf was assessed.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. For AUCinf, 1 participant was excluded from the Moderate Hepatic Impairment group where AUCinf based on extrapolation was greater than 20% and 1 participant was excluded from the Normal Hepatic Function group where Adjusted r-squared value was greater than 0.9.</population>
          <units>ratio</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>MPR AUClast</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.363" spread="0.269"/>
                    <measurement group_id="O2" value="0.653" spread="0.496"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MPR AUCinf</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.428" spread="0.261"/>
                    <measurement group_id="O2" value="0.762" spread="0.467"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.412" spread="0.320"/>
                    <measurement group_id="O2" value="0.881" spread="0.692"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>44.7</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>18.0</ci_lower_limit>
            <ci_upper_limit>111</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>ng*h/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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unbound Quizartinib AUClast</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.8" spread="30.4"/>
                    <measurement group_id="O2" value="84.5" spread="86.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unbound Quizartinib AUCinf</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.4" spread="31.3"/>
                    <measurement group_id="O2" value="88.4" spread="90.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUClast statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>51.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>16.0</ci_lower_limit>
            <ci_upper_limit>165</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>AUCinf statistical comparison was analyzed for Quizartinib.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Least squares (LS) means were calculated from an analysis of variance (ANOVA) model on log-transformed scale. The LS means for each treatment were back transformed from the log scale to provide estimates of the geometric means (GMS). The ratio (%) of GMS was calculated and 90% Confidence Intervals (CIs) for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>51.5</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>15.8</ci_lower_limit>
            <ci_upper_limit>168</ci_upper_limit>
            <estimate_desc>For the comparison, the Moderate Hepatic Impairment treatment group represents the numerator and Normal Hepatic Function treatment group represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. Unbound AC886 concentration were below the level of quantification for 5 participants in the moderate hepatic impairment group and 2 participants in the normal hepatic function group.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set. Unbound AC886 concentration were below the level of quantification for 5 participants in the moderate hepatic impairment group and 2 participants in the normal hepatic function group.</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="1"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0553" spread="NA">Not enough quantifiable data for estimation of standard deviation.</measurement>
                    <measurement group_id="O2" value="0.0658" spread="0.0490"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
        <time_frame>Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>ng*h/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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Unbound AC886 AUClast</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.06" spread="NA">5 participants had concentration below level of detection so there was not enough quantifiable data for estimation of standard deviation.</measurement>
                    <measurement group_id="O2" value="7.17" spread="3.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unbound AC886 AUCinf</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.18" spread="NA">Not enough quantifiable data for estimation of standard deviation.</measurement>
                    <measurement group_id="O2" value="7.35" spread="3.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
        <description>A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.</description>
        <time_frame>Baseline up to 30 days after last dose, up to 2 months</time_frame>
        <population>TEAEs were assessed using the Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Participants With Moderate Hepatic Impairment</title>
            <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Control Participants With Normal Hepatic Function</title>
            <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function</title>
          <description>A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.</description>
          <population>TEAEs were assessed using the Safety Analysis Set.</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 group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the date of signing the informed consent form up to 30 days after last dose, up to 2 months.</time_frame>
      <desc>Adverse events were defined as any untoward, unfavorable, unintended medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. All-cause mortality includes all deaths that occurred during the study and within the 30 days after the last dose of the study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Participants With Moderate Hepatic Impairment</title>
          <description>Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.</description>
        </group>
        <group group_id="E2">
          <title>Control Participants With Normal Hepatic Function</title>
          <description>Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1</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"/>
                <counts group_id="E2" 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"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (24.0)</default_vocab>
        <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="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Contact for Clinical Trial Information</name_or_title>
      <organization>Daiichi Sankyo, Inc.</organization>
      <phone>908-992-6400</phone>
      <email>CTRinfo@dsi.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/NCT04473664
org study id: AC220-A-U105
nct id: NCT04473664
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting
      highly potent and selective but reversible inhibition of Feline McDonough sarcoma (FMS)-like
      tyrosine kinase 3 (FLT3). Quizartinib is currently being studied alone or in combination with
      other agents as a treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome
      (MDS) in adult and pediatric populations.
The primary objective of this study is to determine the plasma pharmacokinetics (PK) of
      quizartinib and its pharmacologically active metabolite AC886 after a single oral dose of 30
      mg in participants with moderate hepatic impairment (HI) (as defined by National Cancer
      Institute-Organ Dysfunction Working Group [NCI-ODWG] criteria) compared to the healthy
      control participants with normal hepatic function.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax) of Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.
measure: Time to Maximum Plasma Concentration (Tmax) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.
measure: Area Under the Plasma Concentration-Time Curve (AUC) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.
measure: Total Apparent Clearance (CL/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Total Apparent Clearance (CL/F) is defined as total apparent clearance and was calculated using non-compartmental analysis.
measure: Volume of Distribution in the Terminal Phase (Vz/F) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Volume of Distribution in the Terminal Phase (Vz/F) is defined as volume of distribution in the terminal phase and was calculated using non-compartmental analysis.
measure: Terminal Half-Life (t1/2) for Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.
measure: Maximum Plasma Concentration (Cmax) of Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.
measure: Time to Maximum Plasma Concentration (Tmax) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was an observed value from the study.
measure: Area Under the Plasma Concentration-Time Curve (AUC) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.
measure: Terminal Half-Life (t1/2) for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Terminal Elimination Half-Life (t1/2) is defined as terminal elimination half-life and was calculated using noncompartmental analysis.
measure: Metabolite to Parent Ratio (MPR) Based on Area Under the Curve for Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: AUCinf is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity and AUClast is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. MPR is defined as a metabolite to parent ratio with metabolite as the numerator and the parent as the denominator. MPR corrected for molecular weight of AC886 of AUCinf and AUClast are reported and were calculated using non-compartmental analysis. AUClast and AUCinf was assessed.
measure: Maximum Plasma Concentration (Cmax) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Quizartinib Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.
measure: Maximum Plasma Concentration (Cmax) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was an observed value for the study.
measure: Area Under the Plasma Concentration-Time Curve (AUC) of Unbound Active Metabolite AC886 Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Day 1 through 22: Predose, 1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 144, 216, 288, 360, 432, and 504 hours post-quizartinib dose
description: Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) is defined as AUC from time 0 to the last measurable concentration, as calculated by the linear up-log down trapezoidal method. Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) is defined as area under the plasma concentration-time curve from the time of dosing extrapolated to infinity. AUClast and AUCinf was assessed.
measure: Number of Participants With Treatment-emergent Adverse Events Following Single Dose of Quizartinib in Participants With Moderate Hepatic Impairment Compared to Participants With Normal Hepatic Function
time frame: Baseline up to 30 days after last dose, up to 2 months
description: A Treatment-Emergent Adverse Events (TEAE) is defined as any event not present prior to the initiation of the drug treatment of the drug treatment or any event already present that worsens in either intensity or frequency following exposure to the drug treatment. Number of any TEAE that is related and unrelated to study medication is presented.
arm group label: Participants with Moderate Hepatic Impairment
arm group type: Experimental
description: Participants with moderate hepatic impairment as defined by NCI-ODWG criteria who received a single, oral dose of quizartinib 30 mg on Day 1.
arm group label: Control Participants with Normal Hepatic Function
arm group type: Experimental
description: Healthy participants with normal hepatic function matched as a group by sex, age (±10 years), and weight (±20%) who received a single, oral dose of quizartinib 30 mg on Day 1.
intervention type: Drug
intervention name: Quizartinib
description: Single oral dose, 30 mg tablet
arm group label: Control Participants with Normal Hepatic Function
arm group label: Participants with Moderate Hepatic Impairment
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Liver Diseases
sharing ipd: Yes
ipd description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
ipd access criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
ipd url: https://vivli.org/ourmember/daiichi-sankyo/
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 