<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/NCT02207725</url>
  </required_header>
  <id_info>
    <org_study_id>14-503</org_study_id>
    <nct_id>NCT02207725</nct_id>
  </id_info>
  <brief_title>A Study in Older Subjects to Evaluate the Safety and Ability of Andexanet Alfa to Reverse the Anticoagulation Effect of Apixaban</brief_title>
  <official_title>A Phase 3 Randomized, Double-Blind, Placebo-controlled Study in Older Subjects to Assess Safety and the Reversal of Apixaban Anticoagulation With Intravenously Administered Andexanet Alfa</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Portola Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Alexion</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this stuy is to evaluate the ability of Andexanet Alfa to reverse the&#xD;
      anticoagulation effect of Apixaban.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">April 2015</primary_completion_date>
  <phase>Phase 3</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)</measure>
    <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
    <description>In Part I, the primary endpoint was percent change from baseline in anti-fXa activity at the nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minutes or +5 minutes time point following the end of the bolus. In Part II, the primary endpoint was the percent change from baseline in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion. The baseline for the primary endpoint in both parts was the anti-fXa activity just prior to administration of andexanet, 3 hours following the Day 4 dose of apixaban. Anti-fXa activity was measured by a modified chromogenic assay.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Part II)</measure>
    <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)</time_frame>
    <description>The percent change from baseline in anti-fXa activity at the nadir, following the bolus, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part II). Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir</measure>
    <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
    <description>Occurrence of ≥80% reduction in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy -Change From Baseline in Free Apixaban Concentration at the Nadir</measure>
    <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
    <description>Change from baseline in free apixaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free apixaban at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Free plasma concentrations of apixaban was determined using a validated method that involved analysis of citrated human plasma with high-throughput equilibrium dialysis followed by liquid chromatography mass spectrometry.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]</measure>
    <time_frame>Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
    <description>Change in ETP from baseline to its peak, where peak was defined as the largest value for ETP between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) {Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo. ETP was measured using a tissue factor-initiated thrombin generation assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)</measure>
    <time_frame>Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
    <description>Number of participants with ETP above the lower limit of the normal range at its peak, between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) [Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. ETP was measured using a tissue factor-initiated thrombin generation assay</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">68</enrollment>
  <condition>Bleeding</condition>
  <arm_group>
    <arm_group_label>Andexanet</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Andexanet (antidote)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Andexanet</intervention_name>
    <arm_group_label>Andexanet</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Reasonably healthy men and women aged 50 to 75&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of abnormal bleeding, active bleeding or risk factors for bleeding&#xD;
&#xD;
          -  History of thrombosis or risk factors for thrombosis&#xD;
&#xD;
          -  History of adult asthma or use of inhaled medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Vandana Mathur, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Portola Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Celerion</name>
      <address>
        <city>Tempe</city>
        <state>Arizona</state>
        <zip>85283</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>April 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 31, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 4, 2014</study_first_posted>
  <results_first_submitted>May 18, 2018</results_first_submitted>
  <results_first_submitted_qc>August 27, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">September 27, 2018</results_first_posted>
  <disposition_first_submitted>September 19, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>September 19, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">September 27, 2017</disposition_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Andexanet alpha</keyword>
  <keyword>Anticoagulation</keyword>
  <keyword>Antidote</keyword>
  <keyword>Apixaban</keyword>
  <keyword>Anti-fXa inhibitor</keyword>
  <keyword>PRT4445</keyword>
  <keyword>Eliquis</keyword>
  <keyword>Reversal agent</keyword>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subject recruitment occurred at investigative site in the US between March 2014 through December 2014</recruitment_details>
      <pre_assignment_details>Apixaban was administered orally at 5 mg twice daily for 3.5 days to steady-state and then administered andexanet as a bolus (400 mg; Part I) or as a bolus followed by an infusion (400 mg bolus followed by 4 mg/min infusion for 120 minutes, 880 mg total dose; Part II). Bolus was started 3 hours after the last apixaban dose.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo (Part I)</title>
          <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
        </group>
        <group group_id="P2">
          <title>Andexanet (Part I)</title>
          <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
        </group>
        <group group_id="P3">
          <title>Placebo (Part II)</title>
          <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
        </group>
        <group group_id="P4">
          <title>Andexanet (Part II)</title>
          <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="9"/>
                <participants group_id="P4" count="25"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="24"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Did Not Receive Treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>33 and 32 subjects were randomized in Part I and Part II of study, respectively</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo (Part I)</title>
          <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
        </group>
        <group group_id="B2">
          <title>Andexanet (Part I)</title>
          <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
        </group>
        <group group_id="B3">
          <title>Placebo (Part II)</title>
          <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
        </group>
        <group group_id="B4">
          <title>Andexanet (Part II)</title>
          <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
        </group>
        <group group_id="B5">
          <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="9"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="24"/>
            <count group_id="B5" value="65"/>
          </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="59.0" spread="3.54"/>
                    <measurement group_id="B2" value="61.0" spread="6.37"/>
                    <measurement group_id="B3" value="59.5" spread="6.91"/>
                    <measurement group_id="B4" value="59.4" spread="7.83"/>
                    <measurement group_id="B5" value="59.9" spread="6.64"/>
                  </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="3"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                    <measurement group_id="B5" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)</title>
        <description>In Part I, the primary endpoint was percent change from baseline in anti-fXa activity at the nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minutes or +5 minutes time point following the end of the bolus. In Part II, the primary endpoint was the percent change from baseline in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion. The baseline for the primary endpoint in both parts was the anti-fXa activity just prior to administration of andexanet, 3 hours following the Day 4 dose of apixaban. Anti-fXa activity was measured by a modified chromogenic assay.</description>
        <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
        <population>Modified Intent-to-Treat Population included all subjects receiving andexanet/placebo with anti-fXa activity baseline value at ≥1 timepoints: 2 or 5 minute after the end of the bolus (Part I; N = 33); 110 minute during continuous infusion, 2 minute before or 5 minute after the end of continuous infusion (Part II; N = 31).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part I)</title>
            <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part I)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O4">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)</title>
          <description>In Part I, the primary endpoint was percent change from baseline in anti-fXa activity at the nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minutes or +5 minutes time point following the end of the bolus. In Part II, the primary endpoint was the percent change from baseline in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion. The baseline for the primary endpoint in both parts was the anti-fXa activity just prior to administration of andexanet, 3 hours following the Day 4 dose of apixaban. Anti-fXa activity was measured by a modified chromogenic assay.</description>
          <population>Modified Intent-to-Treat Population included all subjects receiving andexanet/placebo with anti-fXa activity baseline value at ≥1 timepoints: 2 or 5 minute after the end of the bolus (Part I; N = 33); 110 minute during continuous infusion, 2 minute before or 5 minute after the end of continuous infusion (Part II; N = 31).</population>
          <units>Percent change in anti-fXa activity</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.71" spread="8.559"/>
                    <measurement group_id="O2" value="-93.86" spread="1.650"/>
                    <measurement group_id="O3" value="-32.70" spread="5.578"/>
                    <measurement group_id="O4" value="-92.34" spread="2.809"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>-74.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-78.39</ci_lower_limit>
            <ci_upper_limit>-66.28</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>-59.50</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-64.10</ci_lower_limit>
            <ci_upper_limit>-55.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Part II)</title>
        <description>The percent change from baseline in anti-fXa activity at the nadir, following the bolus, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part II). Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
        <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)</time_frame>
        <population>mITT; 33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Part II)</title>
          <description>The percent change from baseline in anti-fXa activity at the nadir, following the bolus, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part II). Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
          <population>mITT; 33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively.</population>
          <units>Percent change in anti-fXa activity</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.73" spread="4.104"/>
                    <measurement group_id="O2" value="-93.49" spread="1.525"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>-77.14</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-79.98</ci_lower_limit>
            <ci_upper_limit>-74.04</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir</title>
        <description>Occurrence of ≥80% reduction in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
        <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
        <population>mITT; 33 and 31 subjects who received andexanet or placebo were included in the pharmacodynamics (PD) analysis in Part I and II, respectively.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part I)</title>
            <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part I)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O4">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir</title>
          <description>Occurrence of ≥80% reduction in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo</description>
          <population>mITT; 33 and 31 subjects who received andexanet or placebo were included in the pharmacodynamics (PD) analysis in Part I and II, respectively.</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="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy -Change From Baseline in Free Apixaban Concentration at the Nadir</title>
        <description>Change from baseline in free apixaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free apixaban at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Free plasma concentrations of apixaban was determined using a validated method that involved analysis of citrated human plasma with high-throughput equilibrium dialysis followed by liquid chromatography mass spectrometry.</description>
        <time_frame>Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
        <population>54 subjects who received apixaban were included in the apixaban pharmacokinetics (PK) analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part I)</title>
            <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part I)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O4">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy -Change From Baseline in Free Apixaban Concentration at the Nadir</title>
          <description>Change from baseline in free apixaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free apixaban at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Free plasma concentrations of apixaban was determined using a validated method that involved analysis of citrated human plasma with high-throughput equilibrium dialysis followed by liquid chromatography mass spectrometry.</description>
          <population>54 subjects who received apixaban were included in the apixaban pharmacokinetics (PK) analysis</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.854" spread="1.6152"/>
                    <measurement group_id="O2" value="-9.338" spread="3.2043"/>
                    <measurement group_id="O3" value="-2.964" spread="1.1567"/>
                    <measurement group_id="O4" value="-6.480" spread="2.7814"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>-7.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.86</ci_lower_limit>
            <ci_upper_limit>-5.42</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0002</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>-3.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.66</ci_lower_limit>
            <ci_upper_limit>-1.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]</title>
        <description>Change in ETP from baseline to its peak, where peak was defined as the largest value for ETP between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) {Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo. ETP was measured using a tissue factor-initiated thrombin generation assay.</description>
        <time_frame>Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
        <population>33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively; mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part I)</title>
            <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part I)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O4">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]</title>
          <description>Change in ETP from baseline to its peak, where peak was defined as the largest value for ETP between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) {Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo. ETP was measured using a tissue factor-initiated thrombin generation assay.</description>
          <population>33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively; mITT population</population>
          <units>nmol/min</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.182" spread="125.7621"/>
                    <measurement group_id="O2" value="1323.180" spread="335.4321"/>
                    <measurement group_id="O3" value="189.409" spread="184.7842"/>
                    <measurement group_id="O4" value="1193.060" spread="263.3471"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>1227.35</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>984.01</ci_lower_limit>
            <ci_upper_limit>1456.38</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <method>2-sided test exact Wilcoxon rank-sum tes</method>
            <param_type>Hodges-Lehman estimate of shift</param_type>
            <param_value>999.33</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>819.50</ci_lower_limit>
            <ci_upper_limit>1200.53</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)</title>
        <description>Number of participants with ETP above the lower limit of the normal range at its peak, between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) [Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. ETP was measured using a tissue factor-initiated thrombin generation assay</description>
        <time_frame>Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)</time_frame>
        <population>33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively; mITT population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo (Part I)</title>
            <description>Placebo was administered intravenously (IV) as a bolus (Part I). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O2">
            <title>Andexanet (Part I)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute (Part 1). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
          <group group_id="O3">
            <title>Placebo (Part II)</title>
            <description>Placebo was administered IV as a bolus followed by a continuous infusion for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban).</description>
          </group>
          <group group_id="O4">
            <title>Andexanet (Part II)</title>
            <description>Andexanet was administered IV as a bolus of 400 mg at a target rate of approximately 30 mg/minute, followed by a continuous infusion of 480 mg at 4 mg/minute for 120 minutes (Part II). The bolus was started 3 hours after the last apixaban dose (at the approximate steady-state Cmax for apixaban)</description>
          </group>
        </group_list>
        <measure>
          <title>Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)</title>
          <description>Number of participants with ETP above the lower limit of the normal range at its peak, between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) [Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. ETP was measured using a tissue factor-initiated thrombin generation assay</description>
          <population>33 and 31 subjects who received andexanet or placebo were included in the PD analysis in Part I and II, respectively; mITT 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="9"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="24"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>~8 to 12 weeks</time_frame>
      <desc>The Safety Analysis Population consisted of all subjects randomized and treated with study drug (andexanet or placebo)</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo (Part I)</title>
          <description>Vehicle Control</description>
        </group>
        <group group_id="E2">
          <title>Andexanet (Part I)</title>
          <description>400 mg bolus</description>
        </group>
        <group group_id="E3">
          <title>Placebo (Part II)</title>
          <description>Vehicle Control</description>
        </group>
        <group group_id="E4">
          <title>Andexanet (Part II)</title>
          <description>400 mg bolus + 480 mg infusion (4 mg/min)</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vessel Puncture Site Haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vessel Puncture Site Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Vessel Puncture Site Swelling</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="24"/>
              </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="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </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" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="24"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Conducted in healthy volunteers at Clinical Research Organization.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Head of Clinical Development</name_or_title>
      <organization>Portola Pharmaceuticals, Inc.</organization>
      <phone>650-246-7000</phone>
    </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/NCT02207725
org study id: 14-503
nct id: NCT02207725
lead sponsor: 
has dmc: Yes
The purpose of this stuy is to evaluate the ability of Andexanet Alfa to reverse the
      anticoagulation effect of Apixaban.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Parts I and II)
time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)
description: In Part I, the primary endpoint was percent change from baseline in anti-fXa activity at the nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minutes or +5 minutes time point following the end of the bolus. In Part II, the primary endpoint was the percent change from baseline in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion. The baseline for the primary endpoint in both parts was the anti-fXa activity just prior to administration of andexanet, 3 hours following the Day 4 dose of apixaban. Anti-fXa activity was measured by a modified chromogenic assay.
measure: Efficacy: Percent Change From Baseline in Anti-fXa Activity at the Nadir (Part II)
time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part II)
description: The percent change from baseline in anti-fXa activity at the nadir, following the bolus, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part II). Baseline was the last assessment obtained prior to the first dose of andexanet or placebo
measure: Efficacy: Number of Participants With ≥80% Reduction in the Anti-fXa Activity From Baseline to Nadir
time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)
description: Occurrence of ≥80% reduction in anti-fXa activity from its baseline to nadir, when nadir was defined as the smaller value for anti-fXa activity at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo
measure: Efficacy -Change From Baseline in Free Apixaban Concentration at the Nadir
time frame: Baseline to +2 minutes or +5 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)
description: Change from baseline in free apixaban concentration (ng/mL) at the nadir, when nadir was defined as the smaller value for free apixaban at the +2 minute or +5 minute time point after the completion of the andexanet bolus (Part I) or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Free plasma concentrations of apixaban was determined using a validated method that involved analysis of citrated human plasma with high-throughput equilibrium dialysis followed by liquid chromatography mass spectrometry.
measure: Efficacy: Change in Thrombin Generation (ETP) From Baseline to Its Peak [Parts I and II]
time frame: Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)
description: Change in ETP from baseline to its peak, where peak was defined as the largest value for ETP between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) {Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. Baseline was the last assessment obtained prior to the first dose of andexanet or placebo. ETP was measured using a tissue factor-initiated thrombin generation assay.
measure: Efficacy: Number of Participants With Thrombin Generation (ETP) Above the Lower Limit of the Derived Normal Range at Its Peak (mITT Population)
time frame: Baseline to +2 minutes or +10 minutes following the end of andexanet/placebo bolus (Part I), or 10 minutes prior to end of andexanet/placebo continuous infusion or 5 minutes after the end of andexanet/placebo continuous infusion (Part II)
description: Number of participants with ETP above the lower limit of the normal range at its peak, between the +2 minute time point and the +10 minute time point after the end of the andexanet bolus (inclusive) [Part I] or between the 110-minute time point (10 minutes prior to the end of the continuous infusion) and the 5-minute time point after the end of the continuous infusion (inclusive) [Part II]. ETP was measured using a tissue factor-initiated thrombin generation assay
arm group label: Andexanet
arm group type: Experimental
description: Andexanet (antidote)
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Biological
intervention name: Andexanet
arm group label: Andexanet
intervention type: Other
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Vandana Mathur, M.D.
role: Study Director
affiliation: Portola Pharmaceuticals
facility: 
country: United States
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 