<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/NCT02259010</url>
  </required_header>
  <id_info>
    <org_study_id>C14020</org_study_id>
    <secondary_id>U1111-1161-5039</secondary_id>
    <nct_id>NCT02259010</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of Alisertib in Participants With Advanced Solid Tumors or Relapsed/Refractory Lymphoma</brief_title>
  <official_title>A Phase 1 Study to Evaluate the Effect of Itraconazole, a Strong CYP3A Inhibitor, on the Pharmacokinetics of Alisertib (MLN8237) in Adult Patients With Advanced Solid Tumors or Relapsed/Refractory Lymphoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Millennium Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Takeda</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the effect of multi-dose administration of itraconazole on the&#xD;
      single-dose pharmacokinetics (PK) of alisertib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The drug being tested in this study is called alisertib. Alisertib is being tested in adult&#xD;
      participants with advanced solid tumors or relapsed refactory lymphoma. The study will look&#xD;
      at the effect of the pharmacokinetics (how the drug moves through the body) of alisertib in&#xD;
      the presence and absence of itraconazole.&#xD;
&#xD;
      This is an open label study. Participants will receive:&#xD;
&#xD;
        -  Alisertib tablets 30 mg in Part A and 50 mg in Part B&#xD;
&#xD;
        -  Itraconazole oral solution 200 mg in Part A&#xD;
&#xD;
      Participation in Part A is approximately 25 days. Part B participation is repeating 21-day&#xD;
      cycles. The maximum duration of treatment with alisertib will be 12 months (approximately 16&#xD;
      cycles) unless it is determined by the investigator, with agreement by the sponsor, that a&#xD;
      participant would derive clinical benefit from continued treatment beyond 12 months.&#xD;
&#xD;
      This multi-center study will take place in the United States.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 22, 2014</start_date>
  <completion_date type="Actual">October 21, 2016</completion_date>
  <primary_completion_date type="Actual">March 27, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</measure>
    <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
    <description>An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Laboratory Values Reported as AEs</measure>
    <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
    <description>Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change in Weight Reported as AEs</measure>
    <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
    <description>Change relative to baseline in participant's weight measured throughout study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs</measure>
    <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
    <description>Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Advanced Solid Tumors</condition>
  <condition>Relapsed/Refractory Lymphoma</condition>
  <arm_group>
    <arm_group_label>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alisertib</intervention_name>
    <description>Alisertib tablets</description>
    <arm_group_label>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>Itraconazole oral solution</description>
    <arm_group_label>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</arm_group_label>
    <other_name>SPORANOX®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          1. Male and female participants 18 years of age or older.&#xD;
&#xD;
          2. Participants with histologic or cytologic diagnosis of advanced or metastatic solid&#xD;
             tumors or lymphomas for which no curative or life-prolonging therapies exist.&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Systemic treatment with moderate or strong CYP3A inhibitors or inducers must be&#xD;
             discontinued at least 14 days before the first dose of alisertib, and the use of these&#xD;
             agents is not permitted during the study (except for the protocol-specified&#xD;
             administration of itraconazole).&#xD;
&#xD;
          2. Known gastrointestinal (GI) abnormality (including recurrent nausea or vomiting) or GI&#xD;
             procedure that could interfere with or modify the oral absorption or tolerance of&#xD;
             alisertib.&#xD;
&#xD;
          3. Known hypersensitivity or intolerance to itraconazole or similar class agents.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>October 3, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>April 9, 2018</results_first_submitted>
  <results_first_submitted_qc>August 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">September 20, 2019</results_first_posted>
  <last_update_submitted>August 16, 2019</last_update_submitted>
  <last_update_submitted_qc>August 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lymphoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants took part in the study at 4 investigative sites in the United States from 22 October 2014 to 21 October 2016. Data cutoff for the primary analysis was 27 March 2015.</recruitment_details>
      <pre_assignment_details>Participants with a diagnosis of advanced solid tumors or lymphomas were enrolled to receive alisertib 30 mg tablets, orally along with itraconazole 200 mg, oral solution in part A followed by alisertib 50 mg, tablets in part B.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
          <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19">Completed=Completed protocol-specified dosing and PK assessment.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Didn't Completed Dosing; PK Assessment</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and was used for all safety analyses.</population>
      <group_list>
        <group group_id="B1">
          <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
          <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.0" spread="9.52"/>
                  </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="13"/>
                  </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/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="168.3" spread="8.99"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85.55" spread="25.641"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Surface Area</title>
          <description>Body surface area=square root of (height [cm]*weight [kg]/3600).</description>
          <units>m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.983" spread="0.3024"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>Pharmacokinetic (PK) -Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>Pharmacokinetic (PK) -Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
          <units>nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1060.3" spread="403.90"/>
                    <measurement group_id="O2" value="1002.8" spread="263.81"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Least Squares Mean Ratio</param_type>
            <param_value>0.98</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.82</ci_lower_limit>
            <ci_upper_limit>1.19</ci_upper_limit>
            <estimate_desc>Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
          <units>hr*nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15541.6" spread="9119.52"/>
                    <measurement group_id="O2" value="20219.5" spread="9930.93"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Least Squares Mean Ratio</param_type>
            <param_value>1.35</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.02</ci_lower_limit>
            <ci_upper_limit>1.79</ci_upper_limit>
            <estimate_desc>Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here number of participants analyzed are the participants who were evaluable for this outcome measure at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here number of participants analyzed are the participants who were evaluable for this outcome measure at specified time points.</population>
          <units>hr*nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16804.6" spread="9232.87"/>
                    <measurement group_id="O2" value="23488.7" spread="13262.31"/>
                  </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>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <param_type>Least Squares Mean Ratio</param_type>
            <param_value>1.39</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.99</ci_lower_limit>
            <ci_upper_limit>1.95</ci_upper_limit>
            <estimate_desc>Estimates were obtained using a mixed effects model of log (PK parameter) with fixed terms for the itraconazole effect and random terms for participant within period.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
          <units>L/hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.416" spread="2.4007"/>
                    <measurement group_id="O2" value="3.177" spread="1.5765"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters.</population>
          <units>hr</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.920" spread="2.3710" lower_limit="1.07" upper_limit="10.00"/>
                    <measurement group_id="O2" value="2.920" spread="2.0244" lower_limit="1.83" upper_limit="7.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
          <units>hr</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.55" spread="10.316"/>
                    <measurement group_id="O2" value="25.37" spread="9.215"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
          <units>nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Metabolite 1 (M1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="409.4" spread="479.92"/>
                    <measurement group_id="O2" value="450.0" spread="664.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite 2 (M2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="114.0" spread="52.71"/>
                    <measurement group_id="O2" value="103.5" spread="99.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
          <units>hr</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Metabolite 1 (M1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.090" lower_limit="1.00" upper_limit="23.10"/>
                    <measurement group_id="O2" value="3.800" lower_limit="1.98" upper_limit="10.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite 2 (M2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.360" lower_limit="2.95" upper_limit="47.70"/>
                    <measurement group_id="O2" value="23.600" lower_limit="5.73" upper_limit="95.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
        <time_frame>Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm</time_frame>
        <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
          <group group_id="O2">
            <title>Alisertib With Itraconazole</title>
            <description>Itraconazole, 200 mg, oral solution, once daily on Days 5 to 13 along with alisertib 30 mg, tablets, orally, on Day 10 in Part A .</description>
          </group>
        </group_list>
        <measure>
          <title>AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A</title>
          <population>PK-Evaluable Population included participants who completed the protocol-specified dosing at Part A and had sufficient PK assessment to reliably estimate PK parameters. Here, number of participants analyzed are the total number of participants who were evaluable to this outcome measure at specified endpoint.</population>
          <units>hr*nmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Metabolite 1 (M1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10550.8" spread="17276.38"/>
                    <measurement group_id="O2" value="15776.1" spread="29461.34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Metabolite 2 (M2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                    <count group_id="O2" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5880.6" spread="3404.27"/>
                    <measurement group_id="O2" value="5081.6" spread="3334.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <description>An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.</description>
        <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
        <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
            <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <description>An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.</description>
          <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Laboratory Values Reported as AEs</title>
        <description>Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.</description>
        <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
        <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
            <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Laboratory Values Reported as AEs</title>
          <description>Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.</description>
          <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Hypokalemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Elevated blood creatinine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Increased international normalized ratio</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypercalcemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypomagnesemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hypoalbuminemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased blood potassium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased blood sodium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Elevated blood alkaline phosphatase</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Anemia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutropenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Thrombocytopenia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased lymphocyte count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased white blood cell count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Decreased platelet count</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Change in Weight Reported as AEs</title>
        <description>Change relative to baseline in participant's weight measured throughout study.</description>
        <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
        <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
            <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Change in Weight Reported as AEs</title>
          <description>Change relative to baseline in participant's weight measured throughout study.</description>
          <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs</title>
        <description>Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).</description>
        <time_frame>First dose of study drug to 30 days after the last dose of study drug (up to 12 months)</time_frame>
        <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</population>
        <group_list>
          <group group_id="O1">
            <title>Alisertib Without Itraconazole</title>
            <description>Alisertib 30 mg, tablets, orally, on Day 1 in Part A.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs</title>
          <description>Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).</description>
          <population>Safety Population is defined as all participants who received at least 1 dose of any study drug and were used for all safety analyses. Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pyrexia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Palpitations</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Tachycardia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>First dose of study drug up to 30 days after the last dose of study drug (up to 12 months)</time_frame>
      <desc>Although there were 2 parts to the study, however, data for adverse events was not collected separately for each part.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg</title>
          <description>All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 19.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Disease progression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Herpes zoster disseminated</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Glioblastoma</sub_title>
                <description>One treatment-emergent death occurred during treatment and is not related with study drug.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Haemorrhage intracranial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 19.0</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="24" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Leukopenia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Palpitations</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Micturition urgency</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Palmar-plantar erythrodysaesthesia syndrome</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Decubitus ulcer</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Skin hyperpigmentation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="24"/>
              </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>In general, Investigators may publish clinical data after the earlier of (i) publication by the Sponsor or (ii) 12 months following the abandonment, early termination or database lock; provided a copy of the publication provided to Sponsor at least 30 days ahead of publication, the Sponsor's confidential information is removed as may be requested by Sponsor and Investigator defers publication for up to 60 days in the event Sponsor provides notice that it intends to file a patent application.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Director</name_or_title>
      <organization>Takeda</organization>
      <phone>+1-877-825-3327</phone>
      <email>trialdisclosures@takeda.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/NCT02259010
org study id: C14020
secondary id: U1111-1161-5039
nct id: NCT02259010
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study will assess the effect of multi-dose administration of itraconazole on the
      single-dose pharmacokinetics (PK) of alisertib.
The drug being tested in this study is called alisertib. Alisertib is being tested in adult
      participants with advanced solid tumors or relapsed refactory lymphoma. The study will look
      at the effect of the pharmacokinetics (how the drug moves through the body) of alisertib in
      the presence and absence of itraconazole.

      This is an open label study. Participants will receive:

        -  Alisertib tablets 30 mg in Part A and 50 mg in Part B

        -  Itraconazole oral solution 200 mg in Part A

      Participation in Part A is approximately 25 days. Part B participation is repeating 21-day
      cycles. The maximum duration of treatment with alisertib will be 12 months (approximately 16
      cycles) unless it is determined by the investigator, with agreement by the sponsor, that a
      participant would derive clinical benefit from continued treatment beyond 12 months.

      This multi-center study will take place in the United States.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Cmax: Maximum Observed Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUC(Last): Area Under the Plasma Concentration Curve From Time 0 to the Time of the Last Quantifiable Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUC∞: Area Under the Plasma Concentration Curve From Time 0 to Infinity of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: CL/F: Oral Clearance of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Tmax: Time to Reach Maximum Plasma Concentration of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Terminal Phase Elimination Half-Life of Alisertib in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Cmax: Maximum Observed Plasma Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alisertib Metabolites M1 and M2 in Presence and Absence of Itraconazole in Part A
time frame: Day 1 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib without itraconazole arm; Day 10 pre-dose and at multiple time points (up to 96 hours) post-dose in Cycle 1 for alisertib with itraconazole arm
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
description: An AE is considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A SAE is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.
measure: Number of Participants With Abnormal Laboratory Values Reported as AEs
time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
description: Standard safety laboratory tests included Chemistry and Hematology. Abnormal laboratory values that led to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be a clinically significant change from baseline were reported as AEs.
measure: Number of Participants With Clinically Significant Change in Weight Reported as AEs
time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
description: Change relative to baseline in participant's weight measured throughout study.
measure: Number of Participants With Clinically Significant Change in Vital Sign Reported as AEs
time frame: First dose of study drug to 30 days after the last dose of study drug (up to 12 months)
description: Vital signs will include body temperature (oral), sitting blood pressure (after the participant has rested for at least 5 minutes), and pulse (bpm).
arm group label: Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
arm group type: Experimental
description: All participants were to complete Part A prior to Part B. Part A: Alisertib 30 mg, tablets, orally, on Days 1 and 10 plus itraconazole, 200 mg, oral solution, once daily on Days 5 to 13. Part A and B were separated by a washout period of at least 10 days (and up to 4 weeks). Part B: Alisertib 50 mg, tablets, orally, twice daily, for 7 days in 21-day cycles until disease progression or unacceptable toxicity (up to 16 cycles).
intervention type: Drug
intervention name: Alisertib
description: Alisertib tablets
arm group label: Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
intervention type: Drug
intervention name: Itraconazole
description: Itraconazole oral solution
arm group label: Part A: Alisertib 30 mg+Itraconazole; Part B: Alisertib 50 mg
other name: SPORANOX®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Itraconazole
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 