<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/NCT04402866</url>
  </required_header>
  <id_info>
    <org_study_id>0188</org_study_id>
    <secondary_id>2020-001807-18</secondary_id>
    <nct_id>NCT04402866</nct_id>
  </id_info>
  <brief_title>TD-0903 for ALI Associated With COVID-19</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-group, Multi-center Study of an Inhaled Pan-Janus Kinase Inhibitor, TD-0903, to Treat Symptomatic Acute Lung Injury Associated With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Theravance Biopharma</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Theravance Biopharma</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics&#xD;
      of inhaled TD-0903 compared with a matching placebo in combination with standard of care&#xD;
      (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and&#xD;
      impaired oxygenation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Part 1 of the study includes up to 3 ascending dose cohorts, each comprised of 8 subjects (6&#xD;
      receiving TD-0903 and 2 receiving placebo).&#xD;
&#xD;
      Part 2 of the study will evaluate one dose of TD-0903 (selected based on the data from Part&#xD;
      1) as compared with placebo. Part 2 is targeting 198 subjects total.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 24, 2020</start_date>
  <completion_date type="Actual">April 21, 2021</completion_date>
  <primary_completion_date type="Actual">April 21, 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>
    <intervention_model_description>Parallel group, randomized, double-blind, placebo-controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>Pharmacist &amp; Sponsor are not blinded for Part 1. Sponsor is blinded for Part 2. Pharmacist is not blinded for Part 2.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28</measure>
    <time_frame>Randomization to Day 28</time_frame>
    <description>An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.&#xD;
A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7</measure>
    <time_frame>Baseline and Day 7</time_frame>
    <description>SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28</measure>
    <time_frame>Days 7, 14, 21 and 28</time_frame>
    <description>The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:&#xD;
Score 1: Not hospitalized, no limitations on activities&#xD;
Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen&#xD;
Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care&#xD;
Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)&#xD;
Score 5: Hospitalized, requiring supplemental oxygen&#xD;
Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices&#xD;
Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation&#xD;
Score 8: Death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28</measure>
    <time_frame>Day 28</time_frame>
    <description>Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">235</enrollment>
  <condition>Acute Lung Injury (ALI) Associated With COVID-19</condition>
  <condition>Lung Inflammation Associated With COVID-19</condition>
  <arm_group>
    <arm_group_label>Part 1: TD-0903 - MAD Dose A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: TD-0903 - MAD Dose B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: TD-0903 - MAD Dose C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: Placebo for MAD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: TD-0903</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99 subjects will be randomized to receive TD-0903</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>99 subjects will be randomized to receive Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>TD-0903</intervention_name>
    <description>Study Drug to be administered by inhalation</description>
    <arm_group_label>Part 1: TD-0903 - MAD Dose A</arm_group_label>
    <arm_group_label>Part 1: TD-0903 - MAD Dose B</arm_group_label>
    <arm_group_label>Part 1: TD-0903 - MAD Dose C</arm_group_label>
    <arm_group_label>Part 2: TD-0903</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo to be administered by inhalation</description>
    <arm_group_label>Part 1: Placebo for MAD</arm_group_label>
    <arm_group_label>Part 2: Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Willing and able to provide written informed consent on their own prior to performing&#xD;
             study procedures. In the U.K., subject assent or proxy consent as per local site&#xD;
             procedures, may also be acceptable if both a clinician and second health professional&#xD;
             attest that the subject understands the risks and potential benefits of the study and&#xD;
             elects to proceed. Outside the U.K., written informed consent may only be obtained&#xD;
             from the subject or legally authorized representative. In the event the subject loses&#xD;
             capacity during the study, the subject consents to continued participation, except&#xD;
             where this is not clinically indicated.&#xD;
&#xD;
          -  Willing and able to comply with study-related procedures/assessments&#xD;
&#xD;
          -  Age 18 to 80 years old&#xD;
&#xD;
          -  Hospitalized (or documentation of a plan to admit to the hospital if the subject is in&#xD;
             an emergency department) and requiring supplemental oxygen to maintain saturation &gt;&#xD;
             90%&#xD;
&#xD;
          -  A diagnosis of symptomatic COVID-19 defined as a positive test for SARS-CoV-2 RNA&#xD;
             detected by RT-PCR on a sample from the upper respiratory tract (e.g., nasopharyngeal,&#xD;
             nasal, or oropharyngeal swab) collected &lt; 72 hours prior to randomization&#xD;
&#xD;
          -  Onset of COVID-19 -related symptoms &gt; 2 days and &lt;/= 10 days prior to hospital&#xD;
             admission&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects currently receiving invasive mechanical ventilation&#xD;
&#xD;
          -  Presence or suspicion of active malignancy with the exception of cancer in situ (e.g.,&#xD;
             skin cancer)&#xD;
&#xD;
          -  Evidence of serious active infection other than COVID-19&#xD;
&#xD;
          -  Current diagnosis of human immunodeficiency virus, hepatitis B or C&#xD;
&#xD;
          -  In the opinion of the investigator, unlikely to survive for &gt; 24 hours from enrollment&#xD;
&#xD;
          -  Women who are pregnant or might be pregnant, or who are currently breast-feeding.&#xD;
             Subjects must agree to not donate ova or sperm through 30 days after the last dose of&#xD;
             study medication&#xD;
&#xD;
          -  Presence of significant comorbidity that, in the opinion of the investigator,&#xD;
             predisposes the subject to mortality. Such conditions might include: a. New York Heart&#xD;
             Association class IV Heart Failure b. Hepatic dysfunction (i.e., AST or ALT &gt;3x upper&#xD;
             limit of normal) c. Renal dysfunction (i.e., estimated glomerular filtration rate&#xD;
             (eGFR) &lt; 50mL/min) or receiving renal replacement therapy&#xD;
&#xD;
          -  Presence of septic shock at time of enrollment&#xD;
&#xD;
          -  Hemoglobin &lt; 80 g/L&#xD;
&#xD;
          -  Evidence of neutropenia (i.e., absolute neutrophil count &lt; 1000 cells/uL), lymphopenia&#xD;
             (i.e., absolute lymphocyte count &lt; 200 cells/uL) or thrombocytopenia (i.e.Platelets &lt;&#xD;
             50×10^9/L)&#xD;
&#xD;
          -  Hypersensitivity to TD-0903 or its components, or to other JAK inhibitors&#xD;
&#xD;
          -  Treatment with anti-IL 6 (e.g., tocilizumab, sarilumab), anti-IL-6R antagonists (e.g.,&#xD;
             abatacept), JAK inhibitors (e.g., baricitinib, tofacitinib) supplemental interferon&#xD;
             therapy, or tyrosine kinase inhibitors (e.g., erlotinib, gefinitib) in the past 30&#xD;
             days, or plans to receive a JAK inhibitor during the study period&#xD;
&#xD;
          -  Current treatment with conventional synthetic disease-modifying anti-rheumatic drugs&#xD;
             (DMARDs)/immunosuppressive agents including:&#xD;
&#xD;
               1. Methotrexate, cyclosporine, mycophenolate, tacrolimus, penicillamine, or&#xD;
                  sulfasalazine within 2 weeks prior to enrollment&#xD;
&#xD;
               2. Azathioprine or cyclophosphamide within 12 weeks prior to enrollment&#xD;
&#xD;
               3. Monoclonal antibodies targeting B cells (e.g., rituximab) within 12 weeks prior&#xD;
                  to enrollment&#xD;
&#xD;
               4. Tumor necrosis factor-alpha (TNFα)) inhibitors within 4 weeks prior to enrollment&#xD;
&#xD;
          -  Participating in other clinical trials involving any other experimental treatment for&#xD;
             COVID-19, except in the context of a single-arm antiviral or convalescent plasma&#xD;
             compassionate-use protocol&#xD;
&#xD;
          -  Subjects with active or incompletely treated pulmonary tuberculosis, or known history&#xD;
             of non-tuberculosis mycobacterium over past 12 months&#xD;
&#xD;
          -  Subject requires continuous oxygen supplementation for underlying cardio-respiratory&#xD;
             history in the past 90 days&#xD;
&#xD;
          -  Body Mass Index ≥40 kg/m2&#xD;
&#xD;
          -  Receipt of live vaccine (i.e., live attenuated) in the 4 weeks prior to visit 1 or&#xD;
             plans to receive a live vaccine (or live attenuated) during the study period. Note:&#xD;
             Use of non-live (inactivated) vaccinations is allowed for all subjects&#xD;
&#xD;
          -  History of venous thromboembolism (VTE), deep venous thrombosis (DVT), Pulmonary&#xD;
             Embolism (PE) or known hypercoagulable disorder (e.g., factor V Leiden,&#xD;
             antiphospholipid antibody syndrome, protein C or S deficiency)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Monitor</last_name>
    <role>Study Director</role>
    <affiliation>Theravance Biopharma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Sebring</city>
        <state>Florida</state>
        <zip>33870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Fall River</city>
        <state>Massachusetts</state>
        <zip>02720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Kalispell</city>
        <state>Montana</state>
        <zip>59901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Glens Falls</city>
        <state>New York</state>
        <zip>12801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma</name>
      <address>
        <city>Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Bethlehem</city>
        <state>Pennsylvania</state>
        <zip>18015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Wenatchee</city>
        <state>Washington</state>
        <zip>98801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Bela Vista</city>
        <zip>01323-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Botucatu</city>
        <zip>18618-686</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Caxias Do Sul</city>
        <zip>95070-560</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>São José Do Rio Preto</city>
        <zip>15090-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Helsinki</city>
        <zip>00290</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Turku</city>
        <zip>20520</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Chisinau</city>
        <zip>MD-2025</zip>
        <country>Moldova, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>21105</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Brovary</city>
        <zip>07 400</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Kyiv</city>
        <zip>01 103</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Kyiv</city>
        <zip>01 601</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Theravance Biopharma Investigational Site</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9QZ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
    <country>Finland</country>
    <country>Moldova, Republic of</country>
    <country>Romania</country>
    <country>Ukraine</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <results_first_submitted>February 25, 2022</results_first_submitted>
  <results_first_submitted_qc>March 15, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">March 17, 2022</results_first_posted>
  <last_update_submitted>March 15, 2022</last_update_submitted>
  <last_update_submitted_qc>March 15, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Acute lung injury</keyword>
  <keyword>ALI</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Coronavirus Disease 2019</keyword>
  <keyword>inflammatory lung conditions</keyword>
  <keyword>Inflammatory lung disease</keyword>
  <keyword>ARDS</keyword>
  <keyword>SARS-CoV-2</keyword>
  <keyword>Pneumonia</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Pneumonia</mesh_term>
    <mesh_term>Lung Injury</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.</ipd_description>
  </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>September 18, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT04402866/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>December 22, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT04402866/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>235 participants were enrolled across 24 sites in the United States, Brazil, Finland, the Republic of Moldova, Romania, Ukraine and the United Kingdom.</recruitment_details>
      <pre_assignment_details>235 participants were enrolled and 230 participants were randomized and treated with study drug. Within each cohort in Part 1 (multiple-ascending dose design), participants were randomized 3:1, TD-0903 to placebo. During Part 2 (parallel-group design), participants were stratified by baseline age (≤ 60 versus &gt; 60 years), and by concurrent use of antiviral medications (yes or no) at baseline. Within each stratum, participants were randomized 1:1 to receive either TD-0903 or placebo.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Part 1: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="P2">
          <title>Part 1: TD-0903 - 1 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg. Participants were administered a 2 mg loading dose as the total dose on Day 1.</description>
        </group>
        <group group_id="P3">
          <title>Part 1: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
        </group>
        <group group_id="P4">
          <title>Part 1: TD-0903 - 10 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg.</description>
        </group>
        <group group_id="P5">
          <title>Part 2: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="P6">
          <title>Part 2: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="104"/>
                <participants group_id="P6" count="106"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Randomized and Treated With Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="102"/>
                <participants group_id="P6" count="103"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="89"/>
                <participants group_id="P6" count="92"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="15"/>
                <participants group_id="P6" count="14"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Discontinued Prior to Treatment</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="13"/>
                <participants group_id="P6" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Miscellaneous</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Part 1: Safety analysis set - all participants who received at least one dose of study drug.&#xD;
Part 2: Intent-to-Treat (ITT) analysis set - all participants who were randomized into the study.</population>
      <group_list>
        <group group_id="B1">
          <title>Part 1: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="B2">
          <title>Part 1: TD-0903 - 1 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg. Participants were administered a 2 mg loading dose as the total dose on Day 1.</description>
        </group>
        <group group_id="B3">
          <title>Part 1: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
        </group>
        <group group_id="B4">
          <title>Part 1: TD-0903 - 10 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg.</description>
        </group>
        <group group_id="B5">
          <title>Part 2: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="B6">
          <title>Part 2: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
        </group>
        <group group_id="B7">
          <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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="7"/>
            <count group_id="B4" value="6"/>
            <count group_id="B5" value="104"/>
            <count group_id="B6" value="106"/>
            <count group_id="B7" value="235"/>
          </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="70"/>
                    <measurement group_id="B6" value="60"/>
                    <measurement group_id="B7" value="146"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="34"/>
                    <measurement group_id="B6" value="46"/>
                    <measurement group_id="B7" value="89"/>
                  </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="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="41"/>
                    <measurement group_id="B6" value="41"/>
                    <measurement group_id="B7" value="90"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="63"/>
                    <measurement group_id="B6" value="65"/>
                    <measurement group_id="B7" value="145"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="14"/>
                    <measurement group_id="B7" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="90"/>
                    <measurement group_id="B6" value="89"/>
                    <measurement group_id="B7" value="204"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                    <measurement group_id="B6" value="3"/>
                    <measurement group_id="B7" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="102"/>
                    <measurement group_id="B6" value="104"/>
                    <measurement group_id="B7" value="230"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More than one race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28</title>
        <description>An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.&#xD;
A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).</description>
        <time_frame>Randomization to Day 28</time_frame>
        <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Matching Placebo</title>
            <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: TD-0903 - 3 mg</title>
            <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28</title>
          <description>An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.&#xD;
A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).</description>
          <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
          <units>days</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="102"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.0" lower_limit="15.0" upper_limit="23.0"/>
                    <measurement group_id="O2" value="21.0" lower_limit="17.5" upper_limit="23.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.6137</p_value>
            <method>Van Elteren test</method>
            <param_type>Common Odds Ratio</param_type>
            <param_value>1.142</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.706</ci_lower_limit>
            <ci_upper_limit>1.846</ci_upper_limit>
            <estimate_desc>Common Odds Ratio (TD-0903 vs. placebo) and corresponding 95% Wald confidence interval (CI) were obtained from the proportional odds regression model of RFD adjusting for baseline age strata (≤ 60 years vs. &gt; 60 years).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7</title>
        <description>SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.</description>
        <time_frame>Baseline and Day 7</time_frame>
        <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Matching Placebo</title>
            <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: TD-0903 - 3 mg</title>
            <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7</title>
          <description>SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.</description>
          <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
          <units>ratio measure</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="86"/>
                <count group_id="O2" value="90"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="88.97" spread="7.769"/>
                    <measurement group_id="O2" value="88.46" spread="7.654"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.962</p_value>
            <method>Mixed model repeated measures model</method>
            <param_type>LS mean difference</param_type>
            <param_value>-0.51</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-21.95</ci_lower_limit>
            <ci_upper_limit>20.92</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28</title>
        <description>The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:&#xD;
Score 1: Not hospitalized, no limitations on activities&#xD;
Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen&#xD;
Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care&#xD;
Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)&#xD;
Score 5: Hospitalized, requiring supplemental oxygen&#xD;
Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices&#xD;
Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation&#xD;
Score 8: Death</description>
        <time_frame>Days 7, 14, 21 and 28</time_frame>
        <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Matching Placebo</title>
            <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: TD-0903 - 3 mg</title>
            <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28</title>
          <description>The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:&#xD;
Score 1: Not hospitalized, no limitations on activities&#xD;
Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen&#xD;
Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care&#xD;
Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)&#xD;
Score 5: Hospitalized, requiring supplemental oxygen&#xD;
Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices&#xD;
Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation&#xD;
Score 8: Death</description>
          <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</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="102"/>
                <count group_id="O2" value="100"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 7</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Score 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </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="102"/>
                    <count group_id="O2" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Score 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="57"/>
                    <measurement group_id="O2" value="52"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Score 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="72"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="5"/>
                  </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="102"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Score 1</title>
                  <measurement_list>
                    <measurement group_id="O1" value="79"/>
                    <measurement group_id="O2" value="78"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 2</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 3</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 4</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 5</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 6</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 7</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Score 8</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 7</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.5918</p_value>
            <method>Van Elteren test</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.153</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.692</ci_lower_limit>
            <ci_upper_limit>1.922</ci_upper_limit>
            <estimate_desc>Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. &gt; 60 years).</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 14</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.6978</p_value>
            <method>Van Elteren test</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.105</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.651</ci_lower_limit>
            <ci_upper_limit>1.878</ci_upper_limit>
            <other_analysis_desc>Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. &gt; 60 years).</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 21</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.3990</p_value>
            <method>Van Elteren test</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.295</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.702</ci_lower_limit>
            <ci_upper_limit>2.388</ci_upper_limit>
            <other_analysis_desc>Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. &gt; 60 years).</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group on Day 28</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.6445</p_value>
            <method>Van Elteren test</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.180</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.605</ci_lower_limit>
            <ci_upper_limit>2.299</ci_upper_limit>
            <estimate_desc>Between-group comparisons analyzed using a proportional odds model adjusting for baseline age strata (≤ 60 years vs. &gt; 60 years).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28</title>
        <description>Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.</description>
        <time_frame>Day 28</time_frame>
        <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</population>
        <group_list>
          <group group_id="O1">
            <title>Part 2: Matching Placebo</title>
            <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
          </group>
          <group group_id="O2">
            <title>Part 2: TD-0903 - 3 mg</title>
            <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg. Participants were administered a 6 mg loading dose as the total dose on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28</title>
          <description>Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.</description>
          <population>ITT analysis set (Part 2) - all participants with analyzable data who were randomized into the study.</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="104"/>
                <count group_id="O2" value="106"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="85"/>
                    <measurement group_id="O2" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Part 2: TD-0903 - Parallel-Group 3 mg versus Part 2: Matching Placebo - Parallel-Group</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Since this was a Phase 2 study, it was not powered for any of the secondary endpoints.</non_inferiority_desc>
            <p_value>0.3005</p_value>
            <p_value_desc>The p-value was calculated using the Cochran-Mantel-Haenszel chi-square test stratified by baseline age group (≤ 60 years vs. &gt; 60 years)</p_value_desc>
            <method>Cochran-Mantel-Haenszel chi-square test</method>
            <param_type>Risk Difference (RD)</param_type>
            <param_value>5.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.50</ci_lower_limit>
            <ci_upper_limit>14.63</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 to Day 28</time_frame>
      <desc>Safety analysis set - all participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part 1: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="E2">
          <title>Part 1: TD-0903 - 1 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 1 mg.</description>
        </group>
        <group group_id="E3">
          <title>Part 1: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 3 mg.</description>
        </group>
        <group group_id="E4">
          <title>Part 1: TD-0903 - 10 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system at a dose of 10 mg.</description>
        </group>
        <group group_id="E5">
          <title>Part 2: Matching Placebo</title>
          <description>Matching placebo inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system.</description>
        </group>
        <group group_id="E6">
          <title>Part 2: TD-0903 - 3 mg</title>
          <description>TD-0903 inhalation solution (1 mL) was administered once daily for up to 7 days via oral inhalation using the Aerogen Solo nebulizer system. Participants were administered the recommended dose of 3 mg based on the data from Part 1.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 23.1</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="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="13" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="6" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="16" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="10" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Multiple organ dysfunction syndrome</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>COVID-19</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Bacterial sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Systemic bacterial infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 23.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="18" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="15" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Hypertransaminasaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Oropharyngeal candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Vascular device infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depressed mood</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic kidney disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Upper-airway cough syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="103"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="103"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="7"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="6"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="102"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="103"/>
              </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>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Theravance Biopharma</organization>
      <phone>1-855-633-8479</phone>
      <email>medinfo@theravance.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/NCT04402866
org study id: 0188
secondary id: 2020-001807-18
nct id: NCT04402866
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics
      of inhaled TD-0903 compared with a matching placebo in combination with standard of care
      (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and
      impaired oxygenation.
Part 1 of the study includes up to 3 ascending dose cohorts, each comprised of 8 subjects (6
      receiving TD-0903 and 2 receiving placebo).

      Part 2 of the study will evaluate one dose of TD-0903 (selected based on the data from Part
      1) as compared with placebo. Part 2 is targeting 198 subjects total.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Parallel group, randomized, double-blind, placebo-controlled
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: Pharmacist & Sponsor are not blinded for Part 1. Sponsor is blinded for Part 2. Pharmacist is not blinded for Part 2.
measure: Part 2: Number of Respiratory Failure-free Days (RFDs) From Randomization to Day 28
time frame: Randomization to Day 28
description: An RFD was defined as a day that a participant was alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) from randomization through Day 28. The number of RFDs was 0 for participants who used respiratory support for 28 days or longer or for participants who died on or before Day 28.
A clinical status score of ≤ 4 on a given day was equivalent to an RFD. The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. A clinical status score of 4 was defined as a participant who was hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19).
measure: Part 2: Change From Baseline in SaO2/FiO2 Ratio on Day 7
time frame: Baseline and Day 7
description: SaO2/FiO2 ratio was calculated as SaO2 divided by FiO2.
measure: Part 2: Number of Participants in Each Category of the 8-point Ordinal Clinical Status Scale on Days 7, 14, 21, and 28
time frame: Days 7, 14, 21 and 28
description: The clinical status categories and associated scores ranged from 1-8 where a higher score represented a worse outcome. The scale was as follows:
Score 1: Not hospitalized, no limitations on activities
Score 2: Not hospitalized, but with limitations on activities and/or requiring home oxygen
Score 3: Hospitalized, not requiring supplemental oxygen, and no longer requiring ongoing medical care
Score 4: Hospitalized, not requiring supplemental oxygen, but requiring ongoing medical care (whether or not related to COVID-19)
Score 5: Hospitalized, requiring supplemental oxygen
Score 6: Hospitalized, on non-invasive ventilation or high-flow oxygen devices
Score 7: Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation
Score 8: Death
measure: Part 2: Number of Participants Alive and Respiratory Failure-free on Day 28
time frame: Day 28
description: Defined as participants who were alive and did not require the use of any respiratory support (invasive mechanical ventilation, non-invasive positive pressure ventilation, high-flow oxygen devices, or oxygen supplementation) on Day 28.
arm group label: Part 1: TD-0903 - MAD Dose A
arm group type: Experimental
description: 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose A
arm group label: Part 1: TD-0903 - MAD Dose B
arm group type: Experimental
description: 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose B
arm group label: Part 1: TD-0903 - MAD Dose C
arm group type: Experimental
description: 6 out of 8 subjects per cohort will be randomized to receive TD-0903 MAD Dose C
arm group label: Part 1: Placebo for MAD
arm group type: Experimental
description: 2 out of 8 subjects per cohort (up to 3 cohorts) will be randomized to receive placebo
arm group label: Part 2: TD-0903
arm group type: Experimental
description: 99 subjects will be randomized to receive TD-0903
arm group label: Part 2: Placebo
arm group type: Experimental
description: 99 subjects will be randomized to receive Placebo
intervention type: Drug
intervention name: TD-0903
description: Study Drug to be administered by inhalation
arm group label: Part 1: TD-0903 - MAD Dose A
arm group label: Part 1: TD-0903 - MAD Dose B
arm group label: Part 1: TD-0903 - MAD Dose C
arm group label: Part 2: TD-0903
intervention type: Drug
intervention name: Placebo
description: Placebo to be administered by inhalation
arm group label: Part 1: Placebo for MAD
arm group label: Part 2: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Medical Monitor
role: Study Director
affiliation: Theravance Biopharma
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Brazil
country: Finland
country: Moldova, Republic of
country: Romania
country: Ukraine
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Pneumonia
mesh term: Lung Injury
mesh term: Acute Lung Injury
mesh term: Inflammation
sharing ipd: No
ipd description: Theravance Biopharma, Inc. will not be sharing individual de-identified participant data or other relevant study documents.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 