<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/NCT03796013</url>
  </required_header>
  <id_info>
    <org_study_id>GP41049</org_study_id>
    <nct_id>NCT03796013</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Bioequivalence of Two Different Forms of Entrectinib (Forms A and C) Under Fasted Conditions in Healthy Subjects</brief_title>
  <official_title>A Randomized, Open-Label, Two-Treatment, Two-Period, Two-Way Crossover Study to Investigate the Bioequivalence of Entrectinib Polymorph Forms A and C Under Fasted Conditions in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Genentech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Genentech, Inc.</source>
  <oversight_info>
    <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 aims to demonstrate similarities between two different forms of entrectinib (A and&#xD;
      C) when administered under fasted conditions in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">February 6, 2019</completion_date>
  <primary_completion_date type="Actual">February 6, 2019</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 (AUC0-t) of Entrectinib and M5 Metabolite</measure>
    <time_frame>At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite</measure>
    <time_frame>At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</measure>
    <time_frame>Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])</time_frame>
    <description>An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>Form A to Form C Crossover</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first randomized to this arm will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Form C to Form A Crossover</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants first randomized to this arm will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entrectinib Form A</intervention_name>
    <description>Participants will receive a single oral dose of entrectinib form A under fasted conditions.</description>
    <arm_group_label>Form A to Form C Crossover</arm_group_label>
    <arm_group_label>Form C to Form A Crossover</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Entrectinib Form C</intervention_name>
    <description>Participants will receive a single oral dose of entrectinib form C under fasted conditions.</description>
    <arm_group_label>Form A to Form C Crossover</arm_group_label>
    <arm_group_label>Form C to Form A Crossover</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy in the opinion of the investigator. Healthy is defined by the absence of&#xD;
             evidence of any active disease or clinically significant medical condition based on a&#xD;
             detailed medical history and examination&#xD;
&#xD;
          -  Negative test results for Hepatitis B, Hepatitis C, and Human Immunodeficiency Virus&#xD;
             (HIV)&#xD;
&#xD;
          -  Females must not be pregnant or breastfeeding, and females of childbearing potential&#xD;
             will agree to use highly-effective contraception. Females of childbearing potential&#xD;
             must also agree to refrain from donating eggs during the treatment period and for 6&#xD;
             weeks after the final dose of study drug&#xD;
&#xD;
          -  Males must agree to use contraception and to refrain from sperm donation from check-in&#xD;
             (Day -1 of Period 1) to 90 days after the final dose of study drug&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of gastrointestinal surgery or other gastrointestinal disorder that might&#xD;
             affect absorption of medicines from the gastrointestinal tract&#xD;
&#xD;
          -  Presence of a clinically significant disease, illness, medical condition or disorder,&#xD;
             or any other medical history determined by the investigator to be clinically&#xD;
             significant and relevant. Ongoing chronic disorders which are not considered&#xD;
             clinically significant are permissible providing they are stable&#xD;
&#xD;
          -  Clinically significant change in health status, as judged by the investigator, or any&#xD;
             major illness within the 4 weeks before screening, or clinically significant acute&#xD;
             infection or febrile illness within the 14 days before screening&#xD;
&#xD;
          -  Participation in any other clinical study involving an investigational medicinal&#xD;
             product (IMP) or device within 30 days or 5 half-lives (if known), whichever is&#xD;
             longer, before screening&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Covance Research Unit - Dallas</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75247</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>January 4, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 8, 2019</study_first_posted>
  <results_first_submitted>January 27, 2020</results_first_submitted>
  <results_first_submitted_qc>February 25, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2020</results_first_posted>
  <last_update_submitted>February 25, 2020</last_update_submitted>
  <last_update_submitted_qc>February 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Entrectinib</mesh_term>
  </intervention_browse>
  <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>November 5, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03796013/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>January 31, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/13/NCT03796013/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Form A to Form C Crossover</title>
          <description>Participants first randomized to this arm received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
        </group>
        <group group_id="P2">
          <title>Form C to Form A Crossover</title>
          <description>Participants first randomized to this arm received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
              </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>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Form A to Form C Crossover</title>
          <description>Participants first randomized to this arm received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
        </group>
        <group group_id="B2">
          <title>Form C to Form A Crossover</title>
          <description>Participants first randomized to this arm received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1. This dose was followed by a minimum 14-day washout period, after which participants received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 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="14"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="28"/>
          </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="43.9" spread="8.4"/>
                    <measurement group_id="B2" value="44.4" spread="11.7"/>
                    <measurement group_id="B3" value="44" spread="10.4"/>
                  </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="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</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_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="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</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>Multiple</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="20"/>
                  </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 (AUC0-t) of Entrectinib and M5 Metabolite</title>
        <time_frame>At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)</time_frame>
        <population>The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose pharmacokinetic (PK) sample.</population>
        <group_list>
          <group group_id="O1">
            <title>Form A Reference Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
          <group group_id="O2">
            <title>Form C Test Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite</title>
          <population>The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose pharmacokinetic (PK) sample.</population>
          <units>nmol*h/L</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="28"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Entrectinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18500" spread="37.9"/>
                    <measurement group_id="O2" value="16600" spread="30.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M5 metabolite</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3610" spread="37.0"/>
                    <measurement group_id="O2" value="3070" spread="36.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite</title>
        <time_frame>At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)</time_frame>
        <population>The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample.</population>
        <group_list>
          <group group_id="O1">
            <title>Form A Reference Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
          <group group_id="O2">
            <title>Form C Test Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite</title>
          <population>The PK Population consisted of all participants who received at least 1 dose of study drug and had at least 1 evaluable postdose PK sample.</population>
          <units>nmol/L</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="28"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Entrectinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="796" spread="35.6"/>
                    <measurement group_id="O2" value="726" spread="28.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>M5 metabolite</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="138" spread="47.9"/>
                    <measurement group_id="O2" value="114" spread="50.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
        <description>An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])</time_frame>
        <population>The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Form A Reference Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
          <group group_id="O2">
            <title>Form C Test Formulation</title>
            <description>Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)</title>
          <description>An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <population>The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])</time_frame>
      <desc>The Safety Population consisted of all participants who received at least 1 dose of study drug and had at least 1 postdose safety assessment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Form A Reference Formulation</title>
          <description>Participants who received a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 days).</description>
        </group>
        <group group_id="E2">
          <title>Form C Test Formulation</title>
          <description>Participants who received a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 1 and Day 1 of Period 2 (Periods 1 and 2 = 6 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="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Arthropod bite</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
              </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>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800 821-8590</phone>
      <email>genentech@druginfo.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/NCT03796013
org study id: GP41049
nct id: NCT03796013
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This study aims to demonstrate similarities between two different forms of entrectinib (A and
      C) when administered under fasted conditions in healthy subjects.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Concentration-Time Curve (AUC0-t) of Entrectinib and M5 Metabolite
time frame: At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)
measure: Maximum Observed Concentration (Cmax) of Entrectinib and M5 Metabolite
time frame: At pre-defined intervals from Hour 0 through Day 5 of each study Period (Periods 1 and 2 = 6 days)
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
time frame: Baseline through the end of study (up to clinical cut-off date 06 Feb 2019 [28 days])
description: An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
arm group label: Form A to Form C Crossover
arm group type: Experimental
description: Participants first randomized to this arm will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
arm group label: Form C to Form A Crossover
arm group type: Experimental
description: Participants first randomized to this arm will receive a single oral dose of entrectinib form C (test form) under fasted conditions on Day 1 of each Period. This dose will be followed by a minimum 14-day washout period, after which participants will receive a single oral dose of entrectinib form A (reference form) under fasted conditions on Day 1 of Period 2 (Periods 1 and 2 = 6 days).
intervention type: Drug
intervention name: Entrectinib Form A
description: Participants will receive a single oral dose of entrectinib form A under fasted conditions.
arm group label: Form A to Form C Crossover
arm group label: Form C to Form A Crossover
intervention type: Drug
intervention name: Entrectinib Form C
description: Participants will receive a single oral dose of entrectinib form C under fasted conditions.
arm group label: Form A to Form C Crossover
arm group label: Form C to Form A Crossover
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
facility: 
country: United States
responsible party type: Sponsor
mesh term: Entrectinib
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 