<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/NCT03247673</url>
  </required_header>
  <id_info>
    <org_study_id>CT-P16 1.1</org_study_id>
    <nct_id>NCT03247673</nct_id>
  </id_info>
  <brief_title>To Demonstrate Similarity of Pharmacokinetics and Evaluate Safety of CT-P16, EU-Approved Avastin and US-licensed Avastin</brief_title>
  <official_title>A Randomized, Double-blind, Three-arm, Parallel Group, Single-dose Study to Compare the Pharmacokinetics and Safety of Three Formulations of Bevacizumab (CT-P16, EU-approved Avastin and US-licensed Avastin) in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Celltrion</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Celltrion</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a Phase 1 Randomized, Double-blind, Three-arm, Parallel Group, Single-dose&#xD;
      Study to compare the PK, safety and immunogenicity of the proposed biosimilar test product&#xD;
      CT-P16 with EU-approved Avastin and US-licensed Avastin after a single IV infusion of 5mg/kg&#xD;
      of each product to healthy male subjects&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a double-blind, three-arm, parallel group, single-dose study. A total of 141&#xD;
      subjects will be enrolled; 47 subjects in each of the 3 arms of the clinical study. In each&#xD;
      arm, all subjects will receive a single dose (5 mg/kg) of either CT-P16, EU-approved Avastin,&#xD;
      or US-licensed Avastin by intravenous (IV) infusion for 90 min (±5 min) on Day 1 followed by&#xD;
      15 weeks during which the PK, safety, and immunogenicity measurements will be made. The&#xD;
      randomization will be stratified by body weight and site.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 7, 2017</start_date>
  <completion_date type="Actual">January 17, 2018</completion_date>
  <primary_completion_date type="Actual">December 22, 2017</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-inf</measure>
    <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
    <description>Area under the concentration-time curve from time zero to infinity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax</measure>
    <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
    <description>Maximum Serum Concentration (Cmax)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-last</measure>
    <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
    <description>Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Additional Pharmacokinetics (Time to Cmax)</measure>
    <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
    <description>To assess the additional PK of study drugs (Time to Cmax)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Anti-Drug Antibody Positive</measure>
    <time_frame>up to 15 weeks</time_frame>
    <description>number of participants with anti-drug antibody positive at post-dose</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">141</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>CT-P16</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CT-P16 will be administrated once in IV infusion of 5mg/KG to healthy male subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>EU-approved Avastin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>US-licensed Avastin</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CT-P16</intervention_name>
    <description>CT-P16 is a biosimilar product for Avastin</description>
    <arm_group_label>CT-P16</arm_group_label>
    <other_name>bevacizumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>EU-approved Avastin</intervention_name>
    <description>EU-approved Avastin</description>
    <arm_group_label>EU-approved Avastin</arm_group_label>
    <other_name>bevacizumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>US-licensed Avastin</intervention_name>
    <description>US-licensed Avastin</description>
    <arm_group_label>US-licensed Avastin</arm_group_label>
    <other_name>bevacizumab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects between the ages of 19 and 55 years, both inclusive&#xD;
&#xD;
          -  Body Mass Index (BMI) between 18.0 and 29.9 kg/m2 (both inclusive) and a body weight ≥&#xD;
             50 kg&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject is a female.&#xD;
&#xD;
          -  Clinically significant allergic reactions, hypersensitivity&#xD;
&#xD;
          -  A disease classed as significant by the Investigator&#xD;
&#xD;
          -  Non-healing wound, ulcer, bone fracture, a major surgical procedure, significant&#xD;
             traumatic injury&#xD;
&#xD;
          -  Any malignancy&#xD;
&#xD;
          -  Undergone treatment with an investigational drug or participated in another clinical&#xD;
             trial&#xD;
&#xD;
          -  Plans to father a child or donates sperms&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sung Young Lee</last_name>
    <role>Study Director</role>
    <affiliation>Celltrion</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Inje University Busan Paik Hospital</name>
      <address>
        <city>Busan</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inha University Hospital</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul St.Mary's hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <link>
    <url>http://www.celltrion.com</url>
    <description>Celltrion, Inc. homepage</description>
  </link>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 3, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <results_first_submitted>April 8, 2019</results_first_submitted>
  <results_first_submitted_qc>July 17, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 25, 2019</results_first_posted>
  <last_update_submitted>March 25, 2020</last_update_submitted>
  <last_update_submitted_qc>March 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 26, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Immunogenicity</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bevacizumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <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>March 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT03247673/SAP_002.pdf</document_url>
    </provided_document>
    <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>June 7, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT03247673/Prot_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CT-P16</title>
          <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
        </group>
        <group group_id="P2">
          <title>EU-approved Avastin</title>
          <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
        </group>
        <group group_id="P3">
          <title>US-licensed Avastin</title>
          <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="46"/>
                <participants group_id="P2" count="47"/>
                <participants group_id="P3" count="48"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="45"/>
                <participants group_id="P2" count="47"/>
                <participants group_id="P3" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population</population>
      <group_list>
        <group group_id="B1">
          <title>CT-P16</title>
          <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
        </group>
        <group group_id="B2">
          <title>EU-approved Avastin</title>
          <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
        </group>
        <group group_id="B3">
          <title>US-licensed Avastin</title>
          <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
        </group>
        <group group_id="B4">
          <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="46"/>
            <count group_id="B2" value="47"/>
            <count group_id="B3" value="48"/>
            <count group_id="B4" value="141"/>
          </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="28.5" spread="8.69"/>
                    <measurement group_id="B2" value="28.4" spread="7.59"/>
                    <measurement group_id="B3" value="26.5" spread="6.28"/>
                    <measurement group_id="B4" value="27.8" spread="7.57"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="48"/>
                    <measurement group_id="B4" value="141"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="48"/>
                    <measurement group_id="B4" value="141"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </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 group_id="B4" 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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>South Korea</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="48"/>
                    <measurement group_id="B4" value="141"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight (kg)</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.93" spread="9.073"/>
                    <measurement group_id="B2" value="71.01" spread="9.417"/>
                    <measurement group_id="B3" value="69.54" spread="8.141"/>
                    <measurement group_id="B4" value="70.16" spread="8.845"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BMI</title>
          <description>kg/m2</description>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="22.89" spread="2.310"/>
                    <measurement group_id="B2" value="23.20" spread="2.492"/>
                    <measurement group_id="B3" value="23.17" spread="2.303"/>
                    <measurement group_id="B4" value="23.09" spread="2.357"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC0-inf</title>
        <description>Area under the concentration-time curve from time zero to infinity</description>
        <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
        <population>PK population</population>
        <group_list>
          <group group_id="O1">
            <title>CT-P16</title>
            <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
          </group>
          <group group_id="O2">
            <title>EU-approved Avastin</title>
            <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
          </group>
          <group group_id="O3">
            <title>US-licensed Avastin</title>
            <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-inf</title>
          <description>Area under the concentration-time curve from time zero to infinity</description>
          <population>PK population</population>
          <units>h*ug/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42034.90" spread="6070.668"/>
                    <measurement group_id="O2" value="40413.44" spread="5012.778"/>
                    <measurement group_id="O3" value="43017.95" spread="5782.951"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax</title>
        <description>Maximum Serum Concentration (Cmax)</description>
        <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
        <population>PK population</population>
        <group_list>
          <group group_id="O1">
            <title>CT-P16</title>
            <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
          </group>
          <group group_id="O2">
            <title>EU-approved Avastin</title>
            <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
          </group>
          <group group_id="O3">
            <title>US-licensed Avastin</title>
            <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax</title>
          <description>Maximum Serum Concentration (Cmax)</description>
          <population>PK population</population>
          <units>ug/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="117.22" spread="17.756"/>
                    <measurement group_id="O2" value="114.06" spread="15.391"/>
                    <measurement group_id="O3" value="113.09" spread="17.402"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC0-last</title>
        <description>Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration</description>
        <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
        <population>PK population</population>
        <group_list>
          <group group_id="O1">
            <title>CT-P16</title>
            <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
          </group>
          <group group_id="O2">
            <title>EU-approved Avastin</title>
            <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
          </group>
          <group group_id="O3">
            <title>US-licensed Avastin</title>
            <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-last</title>
          <description>Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration</description>
          <population>PK population</population>
          <units>h*ug/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41142.81" spread="5694.184"/>
                    <measurement group_id="O2" value="39411.98" spread="4649.319"/>
                    <measurement group_id="O3" value="41804.05" spread="5463.814"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Additional Pharmacokinetics (Time to Cmax)</title>
        <description>To assess the additional PK of study drugs (Time to Cmax)</description>
        <time_frame>pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI</time_frame>
        <population>PK population</population>
        <group_list>
          <group group_id="O1">
            <title>CT-P16</title>
            <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
          </group>
          <group group_id="O2">
            <title>EU-approved Avastin</title>
            <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
          </group>
          <group group_id="O3">
            <title>US-licensed Avastin</title>
            <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
          </group>
        </group_list>
        <measure>
          <title>Additional Pharmacokinetics (Time to Cmax)</title>
          <description>To assess the additional PK of study drugs (Time to Cmax)</description>
          <population>PK population</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" lower_limit="1.5" upper_limit="12.0"/>
                    <measurement group_id="O2" value="2.5" lower_limit="1.5" upper_limit="8.0"/>
                    <measurement group_id="O3" value="2.5" lower_limit="1.5" upper_limit="8.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Anti-Drug Antibody Positive</title>
        <description>number of participants with anti-drug antibody positive at post-dose</description>
        <time_frame>up to 15 weeks</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>CT-P16</title>
            <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
          </group>
          <group group_id="O2">
            <title>EU-approved Avastin</title>
            <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
          </group>
          <group group_id="O3">
            <title>US-licensed Avastin</title>
            <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Anti-Drug Antibody Positive</title>
          <description>number of participants with anti-drug antibody positive at post-dose</description>
          <population>Safety Population</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="46"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="48"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 15 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>CT-P16</title>
          <description>CT-P16 will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
CT-P16: CT-P16 is a biosimilar product for Avastin</description>
        </group>
        <group group_id="E2">
          <title>EU-approved Avastin</title>
          <description>EU-approved Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
EU-approved Avastin: EU-approved Avastin</description>
        </group>
        <group group_id="E3">
          <title>US-licensed Avastin</title>
          <description>US-licensed Avastin will be administrated once in IV infusion of 5mg/kg to healthy male subjects&#xD;
US-licensed Avastin: US-licensed Avastin</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="46"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (20.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="22" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="17" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Infusion-related reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>Troponin I increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="48"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="48"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="46"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="48"/>
              </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>
    </certain_agreements>
    <limitations_and_caveats>Subject with unreliable PK parameter results were excluded from summary. Only treatment-emergent adverse events were summarized.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Clinical Planning Department Leader</name_or_title>
      <organization>Celltrion</organization>
      <phone>82328505000</phone>
      <email>contact@celltrion.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/NCT03247673
org study id: CT-P16 1.1
nct id: NCT03247673
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study is a Phase 1 Randomized, Double-blind, Three-arm, Parallel Group, Single-dose
      Study to compare the PK, safety and immunogenicity of the proposed biosimilar test product
      CT-P16 with EU-approved Avastin and US-licensed Avastin after a single IV infusion of 5mg/kg
      of each product to healthy male subjects
This study is a double-blind, three-arm, parallel group, single-dose study. A total of 141
      subjects will be enrolled; 47 subjects in each of the 3 arms of the clinical study. In each
      arm, all subjects will receive a single dose (5 mg/kg) of either CT-P16, EU-approved Avastin,
      or US-licensed Avastin by intravenous (IV) infusion for 90 min (±5 min) on Day 1 followed by
      15 weeks during which the PK, safety, and immunogenicity measurements will be made. The
      randomization will be stratified by body weight and site.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: AUC0-inf
time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
description: Area under the concentration-time curve from time zero to infinity
measure: Cmax
time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
description: Maximum Serum Concentration (Cmax)
measure: AUC0-last
time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
description: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration
measure: Additional Pharmacokinetics (Time to Cmax)
time frame: pre-dose, end of infusion, 1 hour after EOI, 4, 8, 12, 24, 48, 72, 168, 336, 672, 1,008, 1,344, 1,680, 2,016, and 2,352 hours after SOI
description: To assess the additional PK of study drugs (Time to Cmax)
measure: Number of Participants With Anti-Drug Antibody Positive
time frame: up to 15 weeks
description: number of participants with anti-drug antibody positive at post-dose
arm group label: CT-P16
arm group type: Experimental
description: CT-P16 will be administrated once in IV infusion of 5mg/KG to healthy male subjects
arm group label: EU-approved Avastin
arm group type: Active Comparator
description: EU-approved Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects
arm group label: US-licensed Avastin
arm group type: Active Comparator
description: US-licensed Avastin will be administrated once in IV infusion of 5mg/KG to healthy male subjects
intervention type: Drug
intervention name: CT-P16
description: CT-P16 is a biosimilar product for Avastin
arm group label: CT-P16
other name: bevacizumab
intervention type: Drug
intervention name: EU-approved Avastin
description: EU-approved Avastin
arm group label: EU-approved Avastin
other name: bevacizumab
intervention type: Drug
intervention name: US-licensed Avastin
description: US-licensed Avastin
arm group label: US-licensed Avastin
other name: bevacizumab
criteria: 
gender: Male
minimum age: 19 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sung Young Lee
role: Study Director
affiliation: Celltrion
facility: 
facility: 
facility: 
country: Korea, Republic of
url: http://www.celltrion.com
description: Celltrion, Inc. homepage
responsible party type: Sponsor
mesh term: Bevacizumab
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Subject with unreliable PK parameter results were excluded from summary. Only treatment-emergent adverse events were summarized.
point of contact: 