<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/NCT03250182</url>
  </required_header>
  <id_info>
    <org_study_id>PT010018</org_study_id>
    <nct_id>NCT03250182</nct_id>
  </id_info>
  <brief_title>A Study to Assess the PK and Safety of PT010 in Subjects With COPD Following Single and Repeat Dose</brief_title>
  <official_title>A Study to Assess the Pharmacokinetics and Safety of PT010 in Subjects With Moderate to Severe COPD Following Single and Repeat Dose Administration</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pearl Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pearl Therapeutics, Inc.</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>
      This is a Phase I open-label, single center study to assess the PK and safety of BGF MDI&#xD;
      320/14.4/9.6 µg in subjects with moderate to severe COPD. Pharmacokinetics will be assessed&#xD;
      following a single dose administration on the first treatment day (Day 1) and will be&#xD;
      assessed again after 7 days of repeat dosing. This study includes a Screening Period of up to&#xD;
      28 days and a single Treatment Period of 8 days. A follow-up phone call will be conducted at&#xD;
      least 5 days but no longer than 7 days after the last dose of study drug.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 11, 2017</start_date>
  <completion_date type="Actual">December 7, 2017</completion_date>
  <primary_completion_date type="Actual">December 7, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Budesonide</measure>
    <time_frame>Day 1</time_frame>
    <description>Maximum plasma concentration (Cmax) - Budesonide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Budesonide</measure>
    <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose</time_frame>
    <description>Maximum plasma concentration (Cmax) - Budesonide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Glycopyrronium</measure>
    <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)</time_frame>
    <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Glycopyrronium</measure>
    <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
    <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Formoterol</measure>
    <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)</time_frame>
    <description>Maximum plasma concentration (Cmax) - Formoterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) - Formoterol</measure>
    <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
    <description>Maximum plasma concentration (Cmax) - Formoterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</measure>
    <time_frame>Day 8</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</measure>
    <time_frame>Day 8</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</measure>
    <time_frame>Day 8</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) - Budesonide</measure>
    <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
    <description>Time to maximum plasma concentration (tmax) - Budesonide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium</measure>
    <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
    <description>Time to maximum plasma concentration (tmax) - Glycopyrronium</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Maximum Plasma Concentration (Tmax) - Formoterol</measure>
    <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
    <description>Time to maximum plasma concentration (tmax) - Formoterol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol</measure>
    <time_frame>Day 1</time_frame>
    <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>PT010</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PT010</intervention_name>
    <description>PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.</description>
    <arm_group_label>PT010</arm_group_label>
    <other_name>PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Given their signed written informed consent to participate.&#xD;
&#xD;
          -  Non-child bearing potential (ie, physiologically incapable of becoming pregnant,&#xD;
             including any female who is 2 years post-menopausal); or Child bearing potential, has&#xD;
             a negative serum pregnancy test at Visit 1, and agrees to acceptable contraceptive&#xD;
             methods used consistently and correctly for the duration of the study.&#xD;
&#xD;
          -  Subjects with an established clinical history of COPD as defined by the American&#xD;
             Thoracic Society (ATS)/European Respiratory Society (ERS), or other local applicable&#xD;
             guidelines.&#xD;
&#xD;
          -  Current or former smokers with a history of at least 10 pack-years of cigarette&#xD;
             smoking.&#xD;
&#xD;
          -  Pre-bronchodilator FEV1/FVC ratio must be &lt;0.70 and pre-bronchodilator FEV1 must be&#xD;
             ≥50% and &lt;80% predicted normal value calculated using National Health and Nutrition&#xD;
             Examination Survey (NHANES) III reference equations&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Significant diseases or conditions to : other than COPD, active pulmonary disease such&#xD;
             as active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis,&#xD;
             primary pulmonary hypertension, interstitial lung disease and uncontrolled sleep apnea&#xD;
             .&#xD;
&#xD;
          -  Women who are pregnant or lactating, or are planning to become pregnant during the&#xD;
             course of the study, or women of childbearing potential who are not using an&#xD;
             acceptable method of contraception.&#xD;
&#xD;
          -  Subjects, who in the opinion of the Investigator, have a current diagnosis of asthma.&#xD;
&#xD;
          -  Subjects who have a history of hypersensitivity to any corticosteroid,&#xD;
&#xD;
          -  β2-agonist, muscarinic anticholinergic, or any component of the MDI&#xD;
&#xD;
          -  Alpha-1 antitrypsin deficiency as the cause of COPD&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul M Dorinsky, MD</last_name>
    <role>Study Director</role>
    <affiliation>Pearl Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>August 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 14, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <results_first_submitted>April 24, 2020</results_first_submitted>
  <results_first_submitted_qc>April 24, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">May 8, 2020</results_first_posted>
  <last_update_submitted>January 12, 2021</last_update_submitted>
  <last_update_submitted_qc>January 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Budesonide</mesh_term>
    <mesh_term>Glycopyrrolate</mesh_term>
    <mesh_term>Formoterol Fumarate</mesh_term>
  </intervention_browse>
  <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>June 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03250182/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 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT03250182/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at a single center in the United States from August 2017 to December 2017.</recruitment_details>
      <pre_assignment_details>BGF MDI 320/14.4/9.6 μg oral inhalation as follows:&#xD;
Single-dose on the morning of Day 1 (Visit 3) followed by serial blood draws for 24 hours&#xD;
BID dosing every morning and evening on Day 2 through Day 7 approximately 12 hours apart&#xD;
Single-dose administration on the morning of Day 8 (Visit 5) followed by serial blood draws for 12 hours</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>PT010</title>
          <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Population: All subjects who received at least 1 dose of study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>PT010</title>
          <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="30"/>
          </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="63.7" spread="7.5"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                  </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 (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Budesonide</title>
        <description>Maximum plasma concentration (Cmax) - Budesonide</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Budesonide</title>
          <description>Maximum plasma concentration (Cmax) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="709.3" spread="57.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Budesonide</title>
        <description>Maximum plasma concentration (Cmax) - Budesonide</description>
        <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Budesonide</title>
          <description>Maximum plasma concentration (Cmax) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="663.2" spread="65.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Glycopyrronium</title>
        <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
        <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Glycopyrronium</title>
          <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.2" spread="80.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Glycopyrronium</title>
        <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
        <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Glycopyrronium</title>
          <description>Maximum plasma concentration (Cmax) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.3" spread="65.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Formoterol</title>
        <description>Maximum plasma concentration (Cmax) - Formoterol</description>
        <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Formoterol</title>
          <description>Maximum plasma concentration (Cmax) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="48.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Plasma Concentration (Cmax) - Formoterol</title>
        <description>Maximum plasma concentration (Cmax) - Formoterol</description>
        <time_frame>Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Plasma Concentration (Cmax) - Formoterol</title>
          <description>Maximum plasma concentration (Cmax) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>pg/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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" spread="38.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2407.3" spread="45.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
        <time_frame>Day 8</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3004.7" spread="58.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.5" spread="45.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
        <time_frame>Day 8</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="23"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73.9" spread="52.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.6" spread="30.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</title>
        <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
        <time_frame>Day 8</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol</title>
          <description>Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="25"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4" spread="30.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide</title>
        <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide</title>
          <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2731.8" spread="45.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium</title>
        <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium</title>
          <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.4" spread="73.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol</title>
        <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol</title>
          <description>Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.4" spread="43.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) - Budesonide</title>
        <description>Time to maximum plasma concentration (tmax) - Budesonide</description>
        <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) - Budesonide</title>
          <description>Time to maximum plasma concentration (tmax) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" lower_limit="0.10" upper_limit="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.67" lower_limit="0.10" upper_limit="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium</title>
        <description>Time to maximum plasma concentration (tmax) - Glycopyrronium</description>
        <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium</title>
          <description>Time to maximum plasma concentration (tmax) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.03" lower_limit="0.03" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="25"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" lower_limit="0.03" upper_limit="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Maximum Plasma Concentration (Tmax) - Formoterol</title>
        <description>Time to maximum plasma concentration (tmax) - Formoterol</description>
        <time_frame>Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Maximum Plasma Concentration (Tmax) - Formoterol</title>
          <description>Time to maximum plasma concentration (tmax) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>hours</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" lower_limit="0.10" upper_limit="9.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="27"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.67" lower_limit="0.03" upper_limit="12.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide</title>
        <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide</title>
          <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="24"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2996.9" spread="41.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium</title>
        <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium</title>
          <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61.2" spread="85.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol</title>
        <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol</description>
        <time_frame>Day 1</time_frame>
        <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>PT010</title>
            <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol</title>
          <description>Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol</description>
          <population>PK Population - All treated subjects who had sufficient data to reliably calculate at least 1 PK parameter for at least one analyte and did not have major protocol deviations which affected the PK analysis.</population>
          <units>h*pg/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="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.0" spread="33.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time of administration of the first dose of study drug to the time of the final follow-up telephone call up to approximately 7 weeks.</time_frame>
      <desc>The Safety Population was defined as all subjects who receive at least 1 dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>PT010</title>
          <description>Budesonide, Glycopyrronium and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) 320/14.4/9.6 µg</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
              </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="5" subjects_at_risk="30"/>
              </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="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Procedural headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscular weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </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>Drafts of any and all publications or presentations that may arise from this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review and approval and to ensure consistency with the policy in this protocol. Pearl Therapeutics will have the right to request appropriate modification to correct facts and to represent its opinions, or the opinions of the publication committee, if these differ with the proposed publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Pearl Therapeutics, Inc.</name_or_title>
      <organization>Pearl Therapeutics, Inc.</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/NCT03250182
org study id: PT010018
nct id: NCT03250182
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase I open-label, single center study to assess the PK and safety of BGF MDI
      320/14.4/9.6 µg in subjects with moderate to severe COPD. Pharmacokinetics will be assessed
      following a single dose administration on the first treatment day (Day 1) and will be
      assessed again after 7 days of repeat dosing. This study includes a Screening Period of up to
      28 days and a single Treatment Period of 8 days. A follow-up phone call will be conducted at
      least 5 days but no longer than 7 days after the last dose of study drug.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Plasma Concentration (Cmax) - Budesonide
time frame: Day 1
description: Maximum plasma concentration (Cmax) - Budesonide
measure: Maximum Plasma Concentration (Cmax) - Budesonide
time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose
description: Maximum plasma concentration (Cmax) - Budesonide
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
description: Maximum plasma concentration (Cmax) - Glycopyrronium
measure: Maximum Plasma Concentration (Cmax) - Glycopyrronium
time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
description: Maximum plasma concentration (Cmax) - Glycopyrronium
measure: Maximum Plasma Concentration (Cmax) - Formoterol
time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose)
description: Maximum plasma concentration (Cmax) - Formoterol
measure: Maximum Plasma Concentration (Cmax) - Formoterol
time frame: Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
description: Maximum plasma concentration (Cmax) - Formoterol
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Budesonide
time frame: Day 8
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Budesonide
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Glycopyrronium
time frame: Day 8
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Glycopyrronium
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
measure: Area Under the Plasma Concentration-time Curve (AUC 0-12) - Formoterol
time frame: Day 8
description: Area under the plasma concentration-time curve from 0 to 12 hours (AUC 0-12) - Formoterol
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Budesonide
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Budesonide
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Glycopyrronium
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Glycopyrronium
measure: Area Under the Plasma Concentration-time Curve (AUC 0-tlast) - Formoterol
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 to the time of the last measurable plasma concentration (AUC 0-tlast) - Formoterol
measure: Time to Maximum Plasma Concentration (Tmax) - Budesonide
time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
description: Time to maximum plasma concentration (tmax) - Budesonide
measure: Time to Maximum Plasma Concentration (Tmax) - Glycopyrronium
time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
description: Time to maximum plasma concentration (tmax) - Glycopyrronium
measure: Time to Maximum Plasma Concentration (Tmax) - Formoterol
time frame: Day 1 (pre-dose 2,6,20,40 minutes, 1,2,4,8,10,12,18,24 hours post-dose), Day 8 (pre-dose and 2,6,20,40 minutes, 1,2,4,8,10,12 hours post-dose)
description: Time to maximum plasma concentration (tmax) - Formoterol
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Budesonide
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Budesonide
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Glycopyrronium
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Glycopyrronium
measure: Area Under the Plasma Concentration-time Curve From 0 Extrapolated to Infinity (AUC0-∞) - Formoterol
time frame: Day 1
description: Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) - Formoterol
arm group label: PT010
arm group type: Experimental
description: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol per protocol. Administered as 2 inhalations per use as instructed in the protocol.
intervention type: Drug
intervention name: PT010
description: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol. Administered as 2 inhalations per use as instructed per the protocol.
arm group label: PT010
other name: PT010; Budesonide, Glycopyrrolate, and Formoterol Fumarate Inhalation Aerosol
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Paul M Dorinsky, MD
role: Study Director
affiliation: Pearl Therapeutics, Inc.
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Budesonide
mesh term: Glycopyrrolate
mesh term: Formoterol Fumarate
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 