<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/NCT04470622</url>
  </required_header>
  <id_info>
    <org_study_id>HTX-019-202</org_study_id>
    <nct_id>NCT04470622</nct_id>
  </id_info>
  <brief_title>Aprepitant Injectable Emulsion in Patients With COVID-19 (GUARDS-1)</brief_title>
  <official_title>A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of Aprepitant Injectable Emulsion in Early Hospitalized Adult Patients With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Heron Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Heron Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study will evaluate the efficacy and safety of aprepitant injectable emulsion added to&#xD;
      standard of care for hospitalized patients with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Study was terminated early by Heron, and was not terminated for safety reasons.&#xD;
  </why_stopped>
  <start_date type="Actual">July 20, 2020</start_date>
  <completion_date type="Actual">June 3, 2021</completion_date>
  <primary_completion_date type="Actual">April 9, 2021</primary_completion_date>
  <phase>Phase 2</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>Proportion of Subjects Alive and Discharged From the Hospital.</measure>
    <time_frame>14 Days.</time_frame>
    <description>ITT Population.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO).</measure>
    <time_frame>56 Days.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Discharge From Hospital.</measure>
    <time_frame>56 Days.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Interleukin 6 (IL-6).</measure>
    <time_frame>Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-emergent Adverse Events.</measure>
    <time_frame>Through Day 56</time_frame>
    <description>Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Treatment Group 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Aprepitant injectable emulsion.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment Group 2</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Saline placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Aprepitant injectable emulsion</intervention_name>
    <description>Aprepitant injectable emulsion, once daily (QD) for 14 days.</description>
    <arm_group_label>Treatment Group 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saline Placebo</intervention_name>
    <description>Saline Placebo, once daily (QD) for 14 days.</description>
    <arm_group_label>Treatment Group 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Is hospitalized for ≤48 hours with SARS-CoV-2 infection. Confirmed by polymerase chain&#xD;
             reaction (PCR), antigen or immunoglobulin M (IgM) antibody test.&#xD;
&#xD;
          -  Has at least 1 of the following: Radiographic infiltrates by imaging, or oxygen&#xD;
             saturation of &lt;94% by pulse oximetry on room air or requiring supplemental oxygen.&#xD;
&#xD;
          -  Not anticipated to require mechanical ventilation within 48 hours.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Is taking high-dose hydroxychloroquine or chloroquine.&#xD;
&#xD;
          -  Is taking pimozide or strong or moderate CYP3A4 inhibitors.&#xD;
&#xD;
          -  Is currently receiving treatment with products intended to modify immune response to&#xD;
             COVID-19 (exception: dexamethasone, methylprednisolone, or equivalent are allowed),&#xD;
             chemotherapy or on hemodialysis or peritoneal dialysis.&#xD;
&#xD;
          -  Has known hypersensitivity to any components of aprepitant injectable emulsion.&#xD;
&#xD;
          -  Has evidence of ARDS.&#xD;
&#xD;
          -  Is being treated with oxygen delivered by high-flow nasal cannula nonrebreather mask,&#xD;
             noninvasive positive pressure ventilation, or ECMO.&#xD;
&#xD;
          -  Has multiple organ failure.&#xD;
&#xD;
          -  Has current confirmed Influenza A or B infection, or a a history of organ or&#xD;
             hematologic transplant, HIV, or active hepatitis B or hepatitis C infection.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Helen Keller Hospital</name>
      <address>
        <city>Sheffield</city>
        <state>Alabama</state>
        <zip>35660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University School of Medicine</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Puerto Rico</country>
  </removed_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>July 13, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 14, 2020</study_first_posted>
  <results_first_submitted>April 8, 2022</results_first_submitted>
  <results_first_submitted_qc>August 8, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">August 30, 2022</results_first_posted>
  <last_update_submitted>August 8, 2022</last_update_submitted>
  <last_update_submitted_qc>August 8, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Coronavirus</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aprepitant</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 11, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT04470622/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 22, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/22/NCT04470622/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>One participant was prematurely randomized while failing screening eligibility. This subject was counted in both 'Screen Failures' and 'Randomized Subjects/ITT population', leading to a discrepancy between the Enrollment number in the Protocol Section (27) and the number of participants Started in the Participant Flow module (26).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
          <description>Aprepitant injectable emulsion, 130 mg once daily (QD) for 14 days.</description>
        </group>
        <group group_id="P2">
          <title>Treatment Group 2: Placebo</title>
          <description>Saline Placebo, QD for 14 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Screen Failure</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" 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>Treatment Group 1: Aprepitant Injectable Emulsion</title>
          <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
        </group>
        <group group_id="B2">
          <title>Treatment Group 2: Placebo</title>
          <description>Saline Placebo, QD for 14 days.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="25"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.8" spread="15.64"/>
                    <measurement group_id="B2" value="57.7" spread="11.93"/>
                    <measurement group_id="B3" value="59.7" spread="13.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Subjects Alive and Discharged From the Hospital.</title>
        <description>ITT Population.</description>
        <time_frame>14 Days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
            <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Treatment Group 2: Placebo</title>
            <description>Saline Placebo, QD for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Subjects Alive and Discharged From the Hospital.</title>
          <description>ITT Population.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO).</title>
        <time_frame>56 Days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
            <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Treatment Group 2: Placebo</title>
            <description>Saline Placebo, QD for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO).</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="2.00" upper_limit="NA">The number of subjects with death or respiratory failure was too small to estimate the median</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="4.00" upper_limit="NA">The number of subjects with death or respiratory failure was too small to estimate the median</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Discharge From Hospital.</title>
        <time_frame>56 Days.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
            <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Treatment Group 2: Placebo</title>
            <description>Saline Placebo, QD for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Discharge From Hospital.</title>
          <units>days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" lower_limit="3.00" upper_limit="8.00"/>
                    <measurement group_id="O2" value="8.0" lower_limit="4.00" upper_limit="11.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Interleukin 6 (IL-6).</title>
        <time_frame>Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))</time_frame>
        <population>Overall Number of Participants Analyzed reflects the Total Enrolled ITT Population whereas Number Analyzed in each row reflects the number of subjects with IL-6 data reported at the specified timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
            <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Treatment Group 2: Placebo</title>
            <description>Saline Placebo, QD for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Interleukin 6 (IL-6).</title>
          <population>Overall Number of Participants Analyzed reflects the Total Enrolled ITT Population whereas Number Analyzed in each row reflects the number of subjects with IL-6 data reported at the specified timepoint.</population>
          <units>pg/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="12"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="12"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.77" spread="26.321"/>
                    <measurement group_id="O2" value="19.11" spread="30.098"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-27.98" spread="42.493"/>
                    <measurement group_id="O2" value="14.83" spread="65.384"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="124.00" spread="NA">The standard deviation is not defined when the sample size is equal to 1.</measurement>
                    <measurement group_id="O2" value="204.30" spread="407.244"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.00" spread="NA">The standard deviation is not defined when the sample size is equal to 1.</measurement>
                    <measurement group_id="O2" value="2.90" spread="NA">The standard deviation is not defined when the sample size is equal to 1.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Discharge</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.41" spread="30.754"/>
                    <measurement group_id="O2" value="-9.68" spread="18.107"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of Treatment-emergent Adverse Events.</title>
        <description>Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.</description>
        <time_frame>Through Day 56</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
            <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
          </group>
          <group group_id="O2">
            <title>Treatment Group 2: Placebo</title>
            <description>Saline Placebo, QD for 14 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of Treatment-emergent Adverse Events.</title>
          <description>Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through Day 56.</time_frame>
      <desc>One subject was prematurely randomized while failing screening eligibility. This subject was counted in both 'Screen Failures' and 'Randomized Subjects/ITT population'. ITT Population includes all subjects who are randomized. Safety Population includes all subjects who received at least one dose of any study drug (including placebo). All-Cause Mortality was assessed in the ITT population. Serious and Other Adverse Events were assessed in the Safety Population.</desc>
      <group_list>
        <group group_id="E1">
          <title>Treatment Group 1: Aprepitant Injectable Emulsion</title>
          <description>Aprepitant injectable emulsion, 130 mg QD for 14 days.</description>
        </group>
        <group group_id="E2">
          <title>Treatment Group 2: Placebo</title>
          <description>Saline Placebo, QD for 14 days.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA, Version 23.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood loss anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus node dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rhabdomyolysis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA, Version 23.0</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="8" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Heparin-induced thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Tongue discomfort</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Leuconostoc infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Anaemia postoperative</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Candida test positive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma muscle</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Pneumomediastinum</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
              <event>
                <sub_title>Subcutaneous emphysema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="13"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Study was terminated early by Heron, and was not terminated for safety reasons. The data reported is only safety data generated from the study.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Sophie Visonneau</name_or_title>
      <organization>Heron Therapeutics, Inc.</organization>
      <phone>858-251-7232</phone>
      <email>svisonneau@herontx.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/NCT04470622
org study id: HTX-019-202
nct id: NCT04470622
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The study will evaluate the efficacy and safety of aprepitant injectable emulsion added to
      standard of care for hospitalized patients with COVID-19.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Proportion of Subjects Alive and Discharged From the Hospital.
time frame: 14 Days.
description: ITT Population.
measure: Time to Death or Respiratory Failure, Defined as Any of the Following: Endotracheal Intubation and Mechanical Ventilation; Oxygen Delivered by High-flow Nasal Cannula; Noninvasive Positive Pressure Ventilation; Extracorporeal Membrane Oxygenation (ECMO).
time frame: 56 Days.
measure: Time to Discharge From Hospital.
time frame: 56 Days.
measure: Change From Baseline in Interleukin 6 (IL-6).
time frame: Days 7, 14, 28, Discharge (from 2 to 43 days; median 6 days (Aprepitant), 8 days (Placebo))
measure: Incidence of Treatment-emergent Adverse Events.
time frame: Through Day 56
description: Number of subjects reporting at least on Treatment-Emergent Adverse Event. Subjects reporting more than one event are counted only once using the highest severity.
arm group label: Treatment Group 1
arm group type: Experimental
description: Aprepitant injectable emulsion.
arm group label: Treatment Group 2
arm group type: Placebo Comparator
description: Saline placebo.
intervention type: Drug
intervention name: Aprepitant injectable emulsion
description: Aprepitant injectable emulsion, once daily (QD) for 14 days.
arm group label: Treatment Group 1
intervention type: Drug
intervention name: Saline Placebo
description: Saline Placebo, once daily (QD) for 14 days.
arm group label: Treatment Group 2
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
country: United States
country: Puerto Rico
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Aprepitant
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Study was terminated early by Heron, and was not terminated for safety reasons. The data reported is only safety data generated from the study.
point of contact: 