<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/NCT04459585</url>
  </required_header>
  <id_info>
    <org_study_id>AC220-A-U104</org_study_id>
    <nct_id>NCT04459585</nct_id>
  </id_info>
  <brief_title>A Study of the Effect of Quizartinib on the Pharmacokinetics of the P-gp Substrate Dabigatran Etexilate in Healthy Participants</brief_title>
  <official_title>A Phase 1, Open-Label, Fixed Sequence Drug Interaction Study to Evaluate the Potential Intestinal Inhibitory Effect of Quizartinib on the Pharmacokinetics of a Pgp Substrate Dabigatran Etexilate in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Daiichi Sankyo Co., Ltd.</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>
      The purpose of this study is to investigate the one-way drug-drug interaction potential of&#xD;
      quizartinib on dabigatran etexilate in healthy adult participants.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the potential intestinal inhibitory effect of quizartinib on the&#xD;
      pharmacokinetics of a Pgp substrate dabigatran etexilate in healthy participants.&#xD;
&#xD;
      The hypothesis for this clinical study is that quizartinib, as a P-gp inhibitor, may increase&#xD;
      the systemic exposure (measured by area under the concentration-time curve [AUC] and maximum&#xD;
      concentration [Cmax]) of P-gp substrates that may be sensitive to intestinal P-gp inhibition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 28, 2020</start_date>
  <completion_date type="Actual">October 20, 2020</completion_date>
  <primary_completion_date type="Actual">October 20, 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</measure>
    <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</measure>
    <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-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 and was calculated using non-compartmental analysis.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</measure>
    <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>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 and was calculated using non-compartmental analysis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</measure>
    <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</measure>
    <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</measure>
    <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</measure>
    <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</measure>
    <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
    <description>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants</measure>
    <time_frame>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>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy Subjects</condition>
  <condition>Drug-drug Interaction</condition>
  <condition>Pharmacokinetics</condition>
  <condition>Quizartinib</condition>
  <arm_group>
    <arm_group_label>Dabigatran + Quizartinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants who will receive a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then will receive a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dabigatran Etexilate Mesylate</intervention_name>
    <description>Single oral 150 mg capsule dose</description>
    <arm_group_label>Dabigatran + Quizartinib</arm_group_label>
    <other_name>Pradaxa</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quizartinib</intervention_name>
    <description>Single oral 60 mg dose of quizartinib administered as two 30 mg tablets (26.5 mg free base per tablet)</description>
    <arm_group_label>Dabigatran + Quizartinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female participants 18 to 55 years of age (inclusive), with a body mass index&#xD;
             (BMI) of 18 kg/m^2 to 32 kg/m^2 (inclusive) and with a minimum body weight of 45 kg at&#xD;
             Screening.&#xD;
&#xD;
          -  In females, documented surgical sterilization, postmenopausal status for at least 1&#xD;
             year (follicle stimulating hormone [FSH] &gt; 40 million international (mIU)/mL serum at&#xD;
             Screening), or agreement to use an approved form of contraception&#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;
          -  Liver function test results must be below the upper limit of normal. Hemoglobin levels&#xD;
             must be ≥ 11.5 g/dL for female participants and ≥ 12.5 g/dL for male participants.&#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;
          -  Presence or history of clinically severe adverse reaction to any drug&#xD;
&#xD;
          -  History of stomach or intestinal surgery or resection that would potentially alter&#xD;
             absorption and/or excretion of orally administered drugs (with the exception of&#xD;
             appendectomy, hernia repair, and/or cholecystectomy)&#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;
          -  History or presence of an abnormal electrocardiogram (ECG), which, in the&#xD;
             investigator's opinion, is clinically significant and/or a QT interval corrected for&#xD;
             heart rate using Fridericia's formula &gt;450 milliseconds (ms) at Screening.&#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 hepatitis C virus [HCV]&#xD;
             (healthy participants), hepatitis A virus (HAV) immunoglobulin M, or anti-human&#xD;
             immunodeficiency virus (HIV) Type 1 and Type 2 (all subjects)&#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;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>Worldwide Clinical Trials</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <results_first_submitted>June 16, 2021</results_first_submitted>
  <results_first_submitted_qc>June 16, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 9, 2021</results_first_posted>
  <last_update_submitted>June 16, 2021</last_update_submitted>
  <last_update_submitted_qc>June 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy subjects</keyword>
  <keyword>Drug-drug Interaction</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Quizartinib</keyword>
  <keyword>P-gp</keyword>
  <keyword>Dabigatran Etexilate</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dabigatran</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>August 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT04459585/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 20 participants who met all inclusion criteria and no exclusion criteria were enrolled from 28 Aug 2020 to 20 Oct 2020 at 1 clinic in the United States.</recruitment_details>
      <pre_assignment_details>This study consisted of two treatment periods. Following a Screening Period of 21 days, eligible participants received only dabigatran etexilate (Reference Treatment) on Day 1 of Period 1 followed by quizartinib and dabigatran etexilate administration (Test Treatment) on Day 5 of Period 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib</title>
          <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 (Day 1 to Day 5)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2 (Day 5 to Day 12)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Baseline characteristics were assessed using the Safety Analysis Set.</population>
      <group_list>
        <group group_id="B1">
          <title>Dabigatran Etexilate/Dabigatran Etexilate + Quizartinib</title>
          <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="39.0" spread="10.37"/>
                  </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="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.</description>
        <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="192" spread="94.5"/>
                    <measurement group_id="O2" value="239" spread="141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Free Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="159" spread="82.2"/>
                    <measurement group_id="O2" value="201" spread="127"/>
                  </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 Total Dabigatran.</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>111.88</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.57</ci_lower_limit>
            <ci_upper_limit>161.35</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) 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>Statistical comparison was analyzed for Free Dabigatran.</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% CIs for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>112.98</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.20</ci_lower_limit>
            <ci_upper_limit>165.34</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</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 and was calculated using non-compartmental analysis.</description>
        <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</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 and was calculated using non-compartmental analysis.</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1720" spread="870"/>
                    <measurement group_id="O2" value="2100" spread="1280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Free Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1390" spread="736"/>
                    <measurement group_id="O2" value="1710" spread="1100"/>
                  </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 Total Dabigatran.</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% CIs for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>111.37</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.51</ci_lower_limit>
            <ci_upper_limit>157.97</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) 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>Statistical comparison was analyzed for Free Dabigatran.</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% CIs for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>111.08</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.35</ci_lower_limit>
            <ci_upper_limit>159.51</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
        <description>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 and was calculated using non-compartmental analysis.</description>
        <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>The pharmacokinetic parameter of Area Under the Plasma Concentration-Time Curve up to Infinity was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
          <description>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 and was calculated using non-compartmental analysis.</description>
          <population>The pharmacokinetic parameter of Area Under the Plasma Concentration-Time Curve up to Infinity was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Dabigatran</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1740" spread="902"/>
                    <measurement group_id="O2" value="2140" spread="1280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Free Dabigatran</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1420" spread="760"/>
                    <measurement group_id="O2" value="1730" spread="1100"/>
                  </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 Total Dabigatran.</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% CIs for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>112.97</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>79.38</ci_lower_limit>
            <ci_upper_limit>160.79</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) 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>Statistical comparison was analyzed for Free Dabigatran.</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% CIs for the ratio (%) of GMS were presented.</non_inferiority_desc>
            <param_type>Ratio (%) of Geometric LS Mean</param_type>
            <param_value>110.72</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>76.77</ci_lower_limit>
            <ci_upper_limit>159.68</ci_upper_limit>
            <estimate_desc>For the comparison, the Dabigatran Etexilate + Quizartinib (Period 2) represents the numerator and Dabigatran Etexilate (Period 1) represents the denominator.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
        <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.</description>
        <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
          <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="1.5" upper_limit="3.1"/>
                    <measurement group_id="O2" value="2.0" lower_limit="1.5" upper_limit="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Free Dabigatran</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.0" lower_limit="1.5" upper_limit="4.0"/>
                    <measurement group_id="O2" value="2.0" lower_limit="1.5" upper_limit="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
        <description>Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.</description>
        <time_frame>Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>The pharmacokinetic parameter of Terminal Elimination Half-Life was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib</title>
          <description>Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.</description>
          <population>The pharmacokinetic parameter of Terminal Elimination Half-Life was assessed using the Pharmacokinetic Analysis Set except for 1 participant that did not meet the protocol inclusion criteria for this analysis.</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total Dabigatran</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.4" spread="4.4"/>
                    <measurement group_id="O2" value="18.1" spread="17.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Free Dabigatran</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                    <count group_id="O2" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.2" spread="4.2"/>
                    <measurement group_id="O2" value="14.1" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
        <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.</description>
        <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
          <description>Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.</description>
          <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
          <units>ng/mL</units>
          <param>Median</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quizartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="250" spread="50.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AC886</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.7" spread="8.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
        <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.</description>
        <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
          <description>Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.</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="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quizartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" lower_limit="2.5" upper_limit="6.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AC886</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.0" lower_limit="3.5" upper_limit="26.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
        <description>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.</description>
        <time_frame>Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)</time_frame>
        <population>Pharmacokinetic parameter was assessed using the Pharmacokinetic Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants</title>
          <description>Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.</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="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Quizartinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9390" spread="1660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AC886</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1350" spread="495"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants</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>Up to 2 months</time_frame>
        <population>TEAEs were assessed using the Safety Analysis Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Period 1: Dabigatran Etexilate</title>
            <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
          </group>
          <group group_id="O2">
            <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
            <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants</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="20"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Related</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unrelated</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </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>Period 1: Dabigatran Etexilate</title>
          <description>Participants who received a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1.</description>
        </group>
        <group group_id="E2">
          <title>Period 2: Dabigatran Etexilate + Quizartinib</title>
          <description>Participants who received a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on Day 5 of Period 2.</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="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.0</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="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="20"/>
              </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/NCT04459585
org study id: AC220-A-U104
nct id: NCT04459585
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to investigate the one-way drug-drug interaction potential of
      quizartinib on dabigatran etexilate in healthy adult participants.
This study will evaluate the potential intestinal inhibitory effect of quizartinib on the
      pharmacokinetics of a Pgp substrate dabigatran etexilate in healthy participants.

      The hypothesis for this clinical study is that quizartinib, as a P-gp inhibitor, may increase
      the systemic exposure (measured by area under the concentration-time curve [AUC] and maximum
      concentration [Cmax]) of P-gp substrates that may be sensitive to intestinal P-gp inhibition.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis.
measure: Area Under the Plasma Concentration-Time Curve up to the Last Quantifiable Concentration Post-Dose (AUClast) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-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 and was calculated using non-compartmental analysis.
measure: Area Under the Plasma Concentration-Time Curve up to Infinity (AUCinf) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: 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 and was calculated using non-compartmental analysis.
measure: Time of Maximum Plasma Concentration (Tmax) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis.
measure: Terminal Elimination Half-Life (T1/2) of Total Dabigatran and of Free Dabigatran Following a Single Dose in Participants Without and With Concomitant Quizartinib
time frame: Period 1 Day 1 (Pre-dose and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60 and 72 hours post-dose) and Period 2 Day 5 (pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Terminal Elimination Half-Life (T1/2) is defined as terminal elimination half-life and was calculated using non-compartmental analysis.
measure: Maximum Plasma Concentration (Cmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Maximum Plasma Concentration (Cmax) is defined as the maximum observed plasma concentration and was calculated using non-compartmental analysis. Cmax was assessed for Quizartinib and Metabolite AC886.
measure: Time of Maximum Plasma Concentration (Tmax) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Time of Maximum Plasma Concentration (Tmax) is defined as time of maximum observed plasma concentration and was calculated using non-compartmental analysis. Tmax was assessed for Quizartinib and Metabolite AC886.
measure: Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) of Quizartinib and the Metabolite ACC886 Following Single Dose of Dabigatran With Quizartinib in Participants
time frame: Period 2 Day 5 (Pre-dose and 1, 2.5, 3, 3.5, 4, 5, 6, 8, 10, 14, 26, 38, 50, 62, and 74 hours post-dose)
description: Area Under the Plasma Concentration-Time Curve From Time 0 to 74 Hours (AUClast,74) is defined as area under the plasma concentration-time curve to the last quantifiable concentration post dose at 74 hours and was calculated using non-compartmental analysis. AUClast,74 was assessed for Quizartinib and Metabolite AC886.
measure: Number of Participants Reporting Treatment-Emergent Adverse Events (TEAE) Relatedness to Study Medication Following Single Dose of Dabigatran Without and With Quizartinib in Participants
time frame: 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: Dabigatran + Quizartinib
arm group type: Experimental
description: Participants who will receive a single oral dose of 150mg dabigatran etexilate on Day 1 of Period 1 and then will receive a single oral dose of 60mg quizartinib 2 hours prior to the administration of a single oral dose of 150mg dabigatran etexilate on the morning of Day 5 of Period 2.
intervention type: Drug
intervention name: Dabigatran Etexilate Mesylate
description: Single oral 150 mg capsule dose
arm group label: Dabigatran + Quizartinib
other name: Pradaxa
intervention type: Drug
intervention name: Quizartinib
description: Single oral 60 mg dose of quizartinib administered as two 30 mg tablets (26.5 mg free base per tablet)
arm group label: Dabigatran + Quizartinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Global Clinical Leader
role: Study Director
affiliation: Daiichi Sankyo, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Dabigatran
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 