<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/NCT04472650</url>
  </required_header>
  <id_info>
    <org_study_id>BGB-Sitravatinib-101</org_study_id>
    <nct_id>NCT04472650</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability of Two Different Capsule Formulations of Sitravatinib in Healthy Adults</brief_title>
  <official_title>A Phase 1, Open-label, Single-dose, Randomized Crossover Study to Evaluate the Relative Bioavailability of Two Different Capsule Formulations of Sitravatinib in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>BeiGene</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>BeiGene</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the study was to investigate the relative bioavailability and&#xD;
      pharmacokinetics (PK) of sitravatinib free base and malate salt capsule formulations&#xD;
      following oral administration in healthy adults.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 23, 2020</start_date>
  <completion_date type="Actual">November 9, 2020</completion_date>
  <primary_completion_date type="Actual">November 9, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-t) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Time of the Maximum Observed Plasma Concentration (Tmax) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Terminal Elimination Half-life (T1/2) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Total Plasma Clearance (CL/F) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Apparent Volume of Distribution (Vz/F) of Sitravatinib</measure>
    <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events</measure>
    <time_frame>Up to Week 8</time_frame>
    <description>Adverse events (AEs) and serious adverse events are defined as an AE that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">26</enrollment>
  <condition>Tumor</condition>
  <arm_group>
    <arm_group_label>Dosing Sequence 1: Sitravatinib Free Base then Malate Salt</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sitravatinib free base capsule 120 mg on Day 1 in Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 in Period 2, with a minimum washout period between dose administrations of 14 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dosing Sequence 2: Sitravatinib Malate Salt then Free Base</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Sitravatinib malate salt capsule 100 mg on Day 1 in Period 1 then sitravatinib free base capsule 120 mg on Day 1 in Period 2, with a minimum washout period between dose administrations of 14 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitravatinib</intervention_name>
    <description>Administered orally as a free base capsule</description>
    <arm_group_label>Dosing Sequence 1: Sitravatinib Free Base then Malate Salt</arm_group_label>
    <arm_group_label>Dosing Sequence 2: Sitravatinib Malate Salt then Free Base</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitravatinib</intervention_name>
    <description>Administered orally as a malate salt capsule</description>
    <arm_group_label>Dosing Sequence 1: Sitravatinib Free Base then Malate Salt</arm_group_label>
    <arm_group_label>Dosing Sequence 2: Sitravatinib Malate Salt then Free Base</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Body mass index between 18.0 and 32.0 kg/m2, inclusive.&#xD;
&#xD;
          2. In good health, determined by no clinically significant findings from medical history,&#xD;
             physical examination, 12-lead ECG, vital sign measurements, and clinical laboratory&#xD;
             evaluations at Screening and/or Check-in as assessed by the Investigator (or&#xD;
             designee).&#xD;
&#xD;
          3. Able to swallow multiple capsules.&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. History of stomach or intestinal surgery or resection&#xD;
&#xD;
          2. Have previously completed or withdrawn from this study or any other study&#xD;
             investigating sitravatinib and have previously received the investigational product.&#xD;
&#xD;
          3. Participants who, in the opinion of the Investigator (or designee), should not&#xD;
             participate in this study.&#xD;
&#xD;
        NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Study Director</last_name>
    <role>Principal Investigator</role>
    <affiliation>BeiGene</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Linear Clinical Research Pty Lt(LCR)</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <results_first_submitted>November 5, 2021</results_first_submitted>
  <results_first_submitted_qc>November 5, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">December 27, 2021</results_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 27, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 12, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT04472650/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 9, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT04472650/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were randomized in a 1:1 ratio in two dosing sequences in a 2-period crossover design at a single site in Australia. Periods 1 and 2 were separated by a minimum of 14 days between dose administrations. Total duration of study participation was up to approximately 8 weeks.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Dosing Sequence 1: Sitravatinib Free Base Capsule Then Malate Salt Capsule</title>
          <description>Sitravatinib free base capsule 120 mg on Day 1 of Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
        <group group_id="P2">
          <title>Dosing Sequence 2: Sitravatinib Malate Salt Capsule Then Free Base Capsule</title>
          <description>Sitravatinib malate salt capsule 100 mg on Day 1 of Period 1 then sitravatinib free base capsule 120 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1 (Up to 15 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period (Minimum 14 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2 (Up to 15 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Analysis Set included participants who received at least 1 dose of sitravatinib</population>
      <group_list>
        <group group_id="B1">
          <title>Dosing Sequence 1: Sitravatinib Free Base Capsule Then Malate Salt Capsule</title>
          <description>Sitravatinib free base capsule 120 mg on Day 1 of Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
        <group group_id="B2">
          <title>Dosing Sequence 2: Sitravatinib Malate Salt Capsule Then Free Base Capsule</title>
          <description>Sitravatinib malate salt capsule 100 mg on Day 1 of Period 1 then sitravatinib free base capsule 120 mg on Day 1 of Period 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="26"/>
          </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="27.1" spread="4.23"/>
                    <measurement group_id="B2" value="28.2" spread="10.19"/>
                    <measurement group_id="B3" value="27.7" spread="7.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2524.7" spread="28.8"/>
                    <measurement group_id="O2" value="2892.6" spread="34.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Sitravatinib Malate Salt Capsule (Test) vs. Sitravatinib Free Base Capsule (Reference). Analysis based on Relative Bioavailability Analysis Set, defined as the subset of participants in the PK Parameters Analysis Set who had at least 1 primary PK parameter (AUC0-t, AUC0-inf and Cmax of sitravatinib) in both periods.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric Least Squares Means</param_type>
            <param_value>87.63</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.273</ci_lower_limit>
            <ci_upper_limit>98.111</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-t) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-t) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>h*ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2458.4" spread="28.2"/>
                    <measurement group_id="O2" value="2821.8" spread="34.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Sitravatinib Malate Salt Capsule (Test) vs. Sitravatinib Free Base Capsule (Reference). Analysis based on Relative Bioavailability Analysis Set, defined as the subset of participants in the PK Parameters Analysis Set who had at least 1 primary PK parameter (AUC0-t, AUC0-inf and Cmax of sitravatinib) in both periods.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric Least Squares Means</param_type>
            <param_value>87.50</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>78.12</ci_lower_limit>
            <ci_upper_limit>98.01</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.96" spread="32.9"/>
                    <measurement group_id="O2" value="62.40" spread="37.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Sitravatinib Malate Salt Capsule (Test) vs. Sitravatinib Free Base Capsule (Reference). Analysis based on Relative Bioavailability Analysis Set, defined as the subset of participants in the PK Parameters Analysis Set who had at least 1 primary PK parameter (AUC0-t, AUC0-inf and Cmax of sitravatinib) in both periods.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio of Geometric Least Squares Means</param_type>
            <param_value>88.80</param_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>77.41</ci_lower_limit>
            <ci_upper_limit>101.87</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Time of the Maximum Observed Plasma Concentration (Tmax) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Time of the Maximum Observed Plasma Concentration (Tmax) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.000" lower_limit="6.00" upper_limit="12.02"/>
                    <measurement group_id="O2" value="8.000" lower_limit="6.00" upper_limit="12.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Terminal Elimination Half-life (T1/2) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Terminal Elimination Half-life (T1/2) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>Hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30.850" lower_limit="21.24" upper_limit="41.88"/>
                    <measurement group_id="O2" value="28.490" lower_limit="22.27" upper_limit="39.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Total Plasma Clearance (CL/F) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Total Plasma Clearance (CL/F) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>Liters/hour</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.61" spread="28.8"/>
                    <measurement group_id="O2" value="41.48" spread="34.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Apparent Volume of Distribution (Vz/F) of Sitravatinib</title>
        <time_frame>Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period</time_frame>
        <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg (test) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Apparent Volume of Distribution (Vz/F) of Sitravatinib</title>
          <population>Pharmacokinetic (PK) parameters analysis set included all participants who received at least 1 dose of sitravatinib and had at least 1 PK parameter of sitravatinib</population>
          <units>Liters</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1733.8" spread="28.7"/>
                    <measurement group_id="O2" value="1780.6" spread="35.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events</title>
        <description>Adverse events (AEs) and serious adverse events are defined as an AE that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters</description>
        <time_frame>Up to Week 8</time_frame>
        <population>Safety Analysis Set included participants who received at least 1 dose of sitravatinib</population>
        <group_list>
          <group group_id="O1">
            <title>Sitravatinib Malate Salt Capsule</title>
            <description>Sitravatinib malate salt capsule 100 mg on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
          <group group_id="O2">
            <title>Sitravatinib Free Base Capsule</title>
            <description>Sitravatinib free base capsule 120 mg on Day 1 of Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events</title>
          <description>Adverse events (AEs) and serious adverse events are defined as an AE that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters</description>
          <population>Safety Analysis Set included participants who received at least 1 dose of sitravatinib</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="25"/>
                <count group_id="O2" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>At least 1 treatment-emergent adverse event (TEAE)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3 or 4 TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious adverse events</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to permanent discontinuation of study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAE leading to death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Week 8</time_frame>
      <desc>Safety Analysis Set included participants who received at least 1 dose of sitravatinib</desc>
      <group_list>
        <group group_id="E1">
          <title>Sitravatinib Malate Salt Capsule</title>
          <description>Sitravatinib malate salt capsule 100 mg on Day 1 in Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
        <group group_id="E2">
          <title>Sitravatinib Free Base Capsule</title>
          <description>Sitravatinib free base capsule 120 mg (reference) on Day 1 in Periods 1 and 2, with a minimum washout period between dose administrations of 14 days</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 23.0</default_vocab>
        <default_assessment>Non-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="10" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Palatal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Catheter site bruise</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Catheter site pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Catheter site related reaction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vessel puncture site bruise</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Vessel puncture site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </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" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
              <event>
                <sub_title>Lethargy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="26"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis contact</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="26"/>
              </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>BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information and may request a further delay to protect its IP rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>BeiGene</organization>
      <phone>+1-877-828-5568</phone>
      <email>clinicaltrials@beigene.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/NCT04472650
org study id: BGB-Sitravatinib-101
nct id: NCT04472650
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The primary objective of the study was to investigate the relative bioavailability and
      pharmacokinetics (PK) of sitravatinib free base and malate salt capsule formulations
      following oral administration in healthy adults.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Concentration-time Curve (AUC) From Time Zero to Infinity (AUC0-∞) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Area Under the Concentration-time Curve From Time Zero to Time of the Last Quantifiable Concentration (AUC0-t) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Maximum Observed Plasma Concentration (Cmax) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Time of the Maximum Observed Plasma Concentration (Tmax) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Apparent Terminal Elimination Half-life (T1/2) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Apparent Total Plasma Clearance (CL/F) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Apparent Volume of Distribution (Vz/F) of Sitravatinib
time frame: Predose and 0.5, 1, 2, 4, 6, 8, 12, 24, 48, 72 and 168 hours postdose in each study period
measure: Number of Participants With Adverse Events
time frame: Up to Week 8
description: Adverse events (AEs) and serious adverse events are defined as an AE that starts during or after the first dose, or starts prior to the first dose and increases in severity after the first dose, including vital signs, physical examination, electrocardiogram, and laboratory parameters
arm group label: Dosing Sequence 1: Sitravatinib Free Base then Malate Salt
arm group type: Experimental
description: Sitravatinib free base capsule 120 mg on Day 1 in Period 1 then sitravatinib malate salt capsule 100 mg on Day 1 in Period 2, with a minimum washout period between dose administrations of 14 days
arm group label: Dosing Sequence 2: Sitravatinib Malate Salt then Free Base
arm group type: Experimental
description: Sitravatinib malate salt capsule 100 mg on Day 1 in Period 1 then sitravatinib free base capsule 120 mg on Day 1 in Period 2, with a minimum washout period between dose administrations of 14 days
intervention type: Drug
intervention name: Sitravatinib
description: Administered orally as a free base capsule
arm group label: Dosing Sequence 1: Sitravatinib Free Base then Malate Salt
arm group label: Dosing Sequence 2: Sitravatinib Malate Salt then Free Base
intervention type: Drug
intervention name: Sitravatinib
description: Administered orally as a malate salt capsule
arm group label: Dosing Sequence 1: Sitravatinib Free Base then Malate Salt
arm group label: Dosing Sequence 2: Sitravatinib Malate Salt then Free Base
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Study Director
role: Principal Investigator
affiliation: BeiGene
facility: 
country: Australia
responsible party type: Sponsor
sharing ipd: Yes
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 