<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/NCT04497948</url>
  </required_header>
  <id_info>
    <org_study_id>D822FC00005</org_study_id>
    <nct_id>NCT04497948</nct_id>
  </id_info>
  <brief_title>Acalabrutinib Study With Best Supportive Care in Participants Hospitalized With COVID-19</brief_title>
  <official_title>An Open-label, Multiple-dose Study of Acalabrutinib, Co Administered With a Proton-pump Inhibitor, in Participants Hospitalized With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Acerta Pharma BV</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Acerta Pharma BV</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study D822FC00005 will investigate the Phamacokinetics, Safety and tolerability of&#xD;
      Acalabrutinib suspension when delivered via a nasogastric tube and co-administered with a&#xD;
      Proton Pump Inhibitor, in the treatment of COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is to support the ongoing clinical development of acalabrutinib (CALQUENCE®) in&#xD;
      hospitalized COVID-19 patients. Because many COVID-19 patients may be unable to swallow&#xD;
      capsules due to respiratory failure (eg, they may require endotracheal intubation for&#xD;
      ventilator support and Naso Gastric tube placement), it is important to have a clinically&#xD;
      acceptable method to administer acalabrutinib (capsules) via NG tube. Furthermore, many&#xD;
      hospitalized patients are placed on high doses of proton pump inhibitors (PPIs) (also&#xD;
      commonly known as antacid medication). This study is designed to determine the Pharmaco&#xD;
      Kinetics (effect of body/ bodily systems on the drug), safety and tolerability of&#xD;
      acalabrutinib suspension, when coadministered with a PPI, in participants with confirmed&#xD;
      SARS-CoV-2 infection requiring hospitalization due to respiratory failure, attributable to&#xD;
      COVID-19 pneumonia and who have an Nasogastric (NG) tube in place.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Data from the CALAVI Phase II trials for Acalabrutinib in patients hospitalized with COVID-19&#xD;
    did not meet their primary efficacy endpoints.&#xD;
&#xD;
    Based on this higher management made the decision to prematurely terminate the D822FC00005 PK&#xD;
    study.&#xD;
  </why_stopped>
  <start_date type="Actual">September 21, 2020</start_date>
  <completion_date type="Actual">November 18, 2020</completion_date>
  <primary_completion_date type="Actual">November 18, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Single group multi dose study. Participants to receive Acalabrutinib + PPI and Best Supportive Care.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</measure>
    <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5</time_frame>
    <description>To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</measure>
    <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5</time_frame>
    <description>To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)</measure>
    <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5)</time_frame>
    <description>To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Single Arm</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Single Arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acalabrutinib</intervention_name>
    <description>Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor</description>
    <arm_group_label>Single Arm</arm_group_label>
    <other_name>CALQUENCE®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant or legally authorized representative must be able to understand the&#xD;
             purpose and risks of the study and provide written informed consent and authorization&#xD;
             to use protected health information (in accordance with national and local patient&#xD;
             privacy regulations).&#xD;
&#xD;
          2. Participants who are hospitalized with coronavirus (SARS-CoV-2) infection, confirmed&#xD;
             by PCR test or other commercial or public health assay in any specimen, as documented&#xD;
             by either of the following:&#xD;
&#xD;
               1. PCR positive in sample collected &lt; 72 hours prior to first dose, OR&#xD;
&#xD;
               2. PCR positive in sample collected ≥ 72 hours prior to first dose (but no more than&#xD;
                  14 days prior to first dose), documented inability to obtain a repeat sample (eg,&#xD;
                  due to lack of testing supplies, limited testing capacity, results taking &gt; 24&#xD;
                  hours, etc), AND progressive disease suggestive of ongoing SARS-CoV-2 infection 3&#xD;
                  Evidence of respiratory failure attributable to COVID-19 pneumonia (documented&#xD;
                  radiographically) before enrollment 4 Nasogastric tube or other types of oral or&#xD;
                  percutaneous gastric feeding tube; placement must be radiographically confirmed&#xD;
                  and expected to remain in place, as judged by the investigator, for a minimum of&#xD;
                  3 days after study enrolment.&#xD;
&#xD;
                  5 Has received treatment with PPIs (eg, omeprazole, esomeprazole, lansoprazole,&#xD;
                  dexlansoprazole, rabeprazole, or pantoprazole) for a minimum of 24 hours&#xD;
                  immediately prior to enrollment; any PPI will be permitted, provided it meets the&#xD;
                  minimum equivalent daily dose of 20 mg rabeprazole.&#xD;
&#xD;
                  Exclusion Criteria:&#xD;
&#xD;
                    1. Any serious and uncorrectable medical condition or abnormality of clinical&#xD;
                       laboratory tests that, in the Investigator's judgment, precludes the&#xD;
                       participant's safe participation in and completion of the study.&#xD;
&#xD;
                    2. In the opinion of the Investigator, progression to death is imminent and&#xD;
                       inevitable within the next 24 hours, irrespective of the provision of&#xD;
                       treatments.&#xD;
&#xD;
                    3. Current refractory nausea and vomiting, malabsorption syndrome, disease&#xD;
                       significantly affecting gastrointestinal function, resection of the stomach,&#xD;
                       extensive small bowel resection that is likely to affect absorption,&#xD;
                       symptomatic inflammatory bowel disease, partial or complete bowel&#xD;
                       obstruction, or gastric restrictions and bariatric surgery, such as gastric&#xD;
                       bypass.&#xD;
&#xD;
                    4. Received BTK inhibitor within 7 days before enrollment.&#xD;
&#xD;
                    5. Requires or is receiving anticoagulation with warfarin or equivalent vitamin&#xD;
                       K antagonists (eg, phenprocoumon) within 7 days prior to enrollment. Other&#xD;
                       anticoagulants are permitted.&#xD;
&#xD;
                    6. Participants on dual antiplatelet and therapeutic anticoagulant therapy (eg,&#xD;
                       aspirin and therapeutic doses of low molecular weight heparin are not&#xD;
                       allowed; however, aspirin and prophylactic/ low doses of&#xD;
                       low-molecular-weight heprin are allowed).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Porto Alegre</city>
        <zip>90035-003</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ribeirão Preto</city>
        <zip>14051-140</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01321-001</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sao Paulo</city>
        <zip>01323-903</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D822FC00005&amp;amp;attachmentIdentifier=07a3f757-baee-4846-9350-9804ab60517d&amp;amp;fileName=D822FC005_CSR_Synopsis_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D822FC00005&amp;amp;attachmentIdentifier=2db78d6d-de17-43c1-bf3e-faab61f41e3a&amp;amp;fileName=D822FC00005_CSP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;amp;parentIdentifier=D822FC00005&amp;amp;attachmentIdentifier=e2ace9db-035d-4763-b419-d5522b9ff114&amp;amp;fileName=D822FC00005_SAP_redacted.pdf&amp;amp;versionIdentifier=</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>June 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <results_first_submitted>October 29, 2021</results_first_submitted>
  <results_first_submitted_qc>October 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 5, 2021</results_first_posted>
  <last_update_submitted>November 16, 2021</last_update_submitted>
  <last_update_submitted_qc>November 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 17, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>2019 novel coronavirus disease</keyword>
  <keyword>Acalabrutinib</keyword>
  <keyword>Btk inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acalabrutinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_time_frame>
    <ipd_access_criteria>When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.</ipd_access_criteria>
    <ipd_url>https://astrazenecagroup-dt.pharmacm.com/DT/Home</ipd_url>
  </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 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT04497948/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>July 16, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT04497948/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Approximately 20 participants were planned to be enrolled to have at least 16 evaluable participants.</recruitment_details>
      <pre_assignment_details>The study enrollment was terminated early due to the termination of the Calquence COVID-19 Clinical development program (LSPC Nov 2020)</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Acalabrutinib + BSC + PPI</title>
          <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Acalabrutinib + BSC + PPI</title>
          <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.3" spread="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>&lt; 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;= 65 years</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>WHITE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BLACK OR AFRICAN AMERICAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AMERICAN INDIAN OR ALASKA NATIVE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ASIAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>OTHER</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>NOT REPORTED</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</title>
        <description>To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI</description>
        <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5</time_frame>
        <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
        <group_list>
          <group group_id="O1">
            <title>Acalabrutinib + BSC + PPI, Visit 1 on Day 1</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Acalabrutinib + BSC + PPI, Visit 2 on Day 2</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.</description>
          </group>
          <group group_id="O3">
            <title>Acalabrutinib + BSC + PPI, Visit 3 on Day 5</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</title>
          <description>To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI</description>
          <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
          <units>h·ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Acalabrutinib</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="524.7" spread="86.5"/>
                    <measurement group_id="O2" value="496.5" spread="58.0"/>
                    <measurement group_id="O3" value="201.1" spread="95.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ACP-5862</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="7"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="832.8" spread="29.3"/>
                    <measurement group_id="O2" value="1228.0" spread="35.1"/>
                    <measurement group_id="O3" value="867.1" spread="43.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</title>
        <description>To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
        <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5</time_frame>
        <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
        <group_list>
          <group group_id="O1">
            <title>Acalabrutinib + BSC + PPI, Visit 1 on Day 1</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.</description>
          </group>
          <group group_id="O2">
            <title>Acalabrutinib + BSC + PPI, Visit 2 on Day 2</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.</description>
          </group>
          <group group_id="O3">
            <title>Acalabrutinib + BSC + PPI, Visit 3 on Day 5</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment on visit 3 on Day 5.</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)</title>
          <description>To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
          <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
          <units>h·ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Acalabrutinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="490.1" spread="64.8"/>
                    <measurement group_id="O2" value="493.7" spread="58.4"/>
                    <measurement group_id="O3" value="193.7" spread="96.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ACP-5862</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="731.0" spread="38.4"/>
                    <measurement group_id="O2" value="1228.0" spread="35.1"/>
                    <measurement group_id="O3" value="827.9" spread="46.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)</title>
        <description>To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
        <time_frame>pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5)</time_frame>
        <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
        <group_list>
          <group group_id="O1">
            <title>Acalabrutinib + BSC + PPI, Visit 1 on Day 1</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 1 on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Acalabrutinib + BSC + PPI, Visit 2 on Day 2</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 2 on Day 2.</description>
          </group>
          <group group_id="O3">
            <title>Acalabrutinib + BSC + PPI, Visit 3 on Day 5</title>
            <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment in visit 3 on Day 5.</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)</title>
          <description>To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI</description>
          <population>Here, number analyzed in each row signifies only the participants with available data that were analyzed for each Acalabrutinib and ACP-5862 analytes.</population>
          <units>ng/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Acalabrutinib</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="297.0" spread="56.7"/>
                    <measurement group_id="O2" value="307.9" spread="51.3"/>
                    <measurement group_id="O3" value="167.1" spread="88.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ACP-5862</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="213.1" spread="62.9"/>
                    <measurement group_id="O2" value="316.9" spread="38.5"/>
                    <measurement group_id="O3" value="324.2" spread="47.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Acalabrutinib + BSC + PPI</title>
          <description>Acalabrutinib with Best Supportive Care also with the Proton-Pump Inhibitor(PPI) treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</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="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Device related infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</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="9" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lymphopenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Fungal infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Klebsiella infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Lower respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pneumonia bacterial</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hepatic enzyme increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Polyneuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Renal impairment</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Laryngospasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Organising pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Dermatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="9"/>
              </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>PI shall provide copies of any materials relating to the Study, or the Developed Technologies that either intends to publish or make any presentations relating to, at least 30 days in advance of publication, submission or presentation.&#xD;
PI shall not include in or shall remove from any proposed publication of any Confidential Information, errors or inaccuracies; and shall withhold publication, submission for publication or presentation for 90 days from the date the Company receives the material.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Information Center</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>1-877-240-9479</phone>
      <email>information.center@astrazeneca.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/NCT04497948
org study id: D822FC00005
nct id: NCT04497948
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
Study D822FC00005 will investigate the Phamacokinetics, Safety and tolerability of
      Acalabrutinib suspension when delivered via a nasogastric tube and co-administered with a
      Proton Pump Inhibitor, in the treatment of COVID-19.
This study is to support the ongoing clinical development of acalabrutinib (CALQUENCE®) in
      hospitalized COVID-19 patients. Because many COVID-19 patients may be unable to swallow
      capsules due to respiratory failure (eg, they may require endotracheal intubation for
      ventilator support and Naso Gastric tube placement), it is important to have a clinically
      acceptable method to administer acalabrutinib (capsules) via NG tube. Furthermore, many
      hospitalized patients are placed on high doses of proton pump inhibitors (PPIs) (also
      commonly known as antacid medication). This study is designed to determine the Pharmaco
      Kinetics (effect of body/ bodily systems on the drug), safety and tolerability of
      acalabrutinib suspension, when coadministered with a PPI, in participants with confirmed
      SARS-CoV-2 infection requiring hospitalization due to respiratory failure, attributable to
      COVID-19 pneumonia and who have an Nasogastric (NG) tube in place.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Single group multi dose study. Participants to receive Acalabrutinib + PPI and Best Supportive Care.
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Concentration-time Curve From 0 to 12 Hours (AUC12h) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)
time frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day 5
description: To summarize the PK parameter AUC12h of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC + PPI
measure: Area Under the Concentration-time Curve From 0 to Time to Last Quantifiable Concentration (AUClast) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2 (Day 2), and Visit 3 (Day 5)
time frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1 on Day 1, visit 2 on Day 2 and visit 3 on Day5
description: To summarize the PK parameter AUClast for Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
measure: Maximum Observed Plasma Concentration (Cmax) for Acalabrutinib and ACP-5862 in Visit 1 (Day 1), Visit 2(Day2) and Visit 3 (Day 5)
time frame: pre-dose and 0.5, 1, 2, 4, 6, and 12 hours in visit 1(Day 1), visit 2(Day 2) and visit 3(Day 5)
description: To summarize the PK parameter Cmax of Acalabrutinib/ACP-5862 in single arm, Acalabrutinib + BSC +PPI
arm group label: Single Arm
arm group type: Other
description: Single Arm
intervention type: Drug
intervention name: Acalabrutinib
description: Acalabrutinib (CALQUENCE®) is a covalent BTK inhibitor
arm group label: Single Arm
other name: CALQUENCE®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: Brazil
country: United States
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D822FC00005&amp;attachmentIdentifier=07a3f757-baee-4846-9350-9804ab60517d&amp;fileName=D822FC005_CSR_Synopsis_redacted.pdf&amp;versionIdentifier=
description: Related Info
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D822FC00005&amp;attachmentIdentifier=2db78d6d-de17-43c1-bf3e-faab61f41e3a&amp;fileName=D822FC00005_CSP_redacted.pdf&amp;versionIdentifier=
description: Related Info
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&amp;parentIdentifier=D822FC00005&amp;attachmentIdentifier=e2ace9db-035d-4763-b419-d5522b9ff114&amp;fileName=D822FC00005_SAP_redacted.pdf&amp;versionIdentifier=
description: Related Info
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Acalabrutinib
sharing ipd: Yes
ipd description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd access criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
ipd url: https://astrazenecagroup-dt.pharmacm.com/DT/Home
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 