<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/NCT02196077</url>
  </required_header>
  <id_info>
    <org_study_id>PT009001</org_study_id>
    <nct_id>NCT02196077</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety Study of PT009, PT008, and PT005 in Subjects With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <acronym>PT009001</acronym>
  <official_title>A Randomized, Double Blind, Chronic Dosing (28 Days), Four Period, Five Treatment, Incomplete Block, Multi Center, Crossover Study to Assess the Efficacy and Safety of PT009, PT008, and PT005 in Subjects With Moderate to Severe COPD</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 IIb, randomized, double blind, chronic dosing (28 days), four period, five&#xD;
      treatment, incomplete block, crossover design in subjects with moderate to severe COPD. The&#xD;
      overall objective is to demonstrate that the combination of budesonide (BD; PT008) and&#xD;
      formoterol fumarate (FF; PT005) in a metered-dose inhaler (MDI); (BFF MDI; PT009) provides&#xD;
      benefit on lung function compared with BD MDI in subjects with moderate to severe COPD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2014</start_date>
  <completion_date type="Actual">March 1, 2015</completion_date>
  <primary_completion_date type="Actual">March 1, 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>FEV1 AUC0-12 on Day 29</measure>
    <time_frame>Day 29</time_frame>
    <description>Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days</measure>
    <time_frame>Over 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change From Baseline in FEV1 (in Liters) Day 15</measure>
    <time_frame>Day 15</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change From Baseline in FEV1 (in Liters) Day 29</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change From Baseline in FEV1 on Day 1</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced Vital Capacity (FVC) AUC0-12 on Day 29</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transition Dyspnea Index (TDI) Focal Score on Day 29</measure>
    <time_frame>Day 29</time_frame>
    <description>Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment</measure>
    <time_frame>Visit 12-13 (7 days)</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">180</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>BFF MDI 320/9.6 μg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BFF MDI 160/9.6 μg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI)160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BFF MDI 80/9.6 μg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BD MDI 320 μg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>FF MDI 9.6 μg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BFF MDI 320/9.6 μg</intervention_name>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
    <arm_group_label>BFF MDI 320/9.6 μg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BFF MDI 160/9.6 μg</intervention_name>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
    <arm_group_label>BFF MDI 160/9.6 μg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BFF MDI 80/9.6 μg</intervention_name>
    <description>Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)</description>
    <arm_group_label>BFF MDI 80/9.6 μg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BD MDI 320 μg</intervention_name>
    <description>Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)</description>
    <arm_group_label>BD MDI 320 μg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>FF MDI 9.6 μg</intervention_name>
    <description>Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)</description>
    <arm_group_label>FF MDI 9.6 μg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Informed Consent Form (ICF) prior to any study related procedures&#xD;
&#xD;
          -  COPD Diagnosis: Subjects with an established clinical history of COPD as defined by&#xD;
             the American Thoracic Society (ATS)/European Respiratory Society (ERS)&#xD;
&#xD;
          -  Tobacco Use: Current or former smokers with a history of at least 10 pack years of&#xD;
             cigarette smoking&#xD;
&#xD;
          -  Women of non-childbearing potential or medically acceptable contraception for women of&#xD;
             child-bearing potential and males with female partners of childbearing potential&#xD;
&#xD;
          -  Severity of Disease: Subjects with an established clinical history of COPD and&#xD;
             severity defined as: FEV1/forced vital capacity (FVC) ratio of &lt;0.70; At Screening&#xD;
             (Visit 1a/b), post bronchodilator FEV1 must be &lt;80% predicted normal value, calculated&#xD;
             using NHANES III (Third National Health and Nutrition Examination Survey) reference&#xD;
             equations; the measured FEV1 must also be ≥30% of predicted normal value; at Visit 2,&#xD;
             the average of the 60 minutes and 30 minutes pre dose FEV1 assessments must be &lt;80%&#xD;
             predicted normal value calculated using NHANES III reference equations&#xD;
&#xD;
          -  Screening clinical laboratory tests must be acceptable to the Investigator&#xD;
&#xD;
          -  Screening ECG must be acceptable to the Investigator&#xD;
&#xD;
          -  Chest x ray or computerized tomography (CT) scan within 6 months prior to Visit 1a&#xD;
             must be acceptable to the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Significant diseases other than COPD, ie., disease or condition which, in the opinion&#xD;
             of the Investigator, may put the subject at risk because of participation in the study&#xD;
             or may influence either the results of the study or the subject's ability to&#xD;
             participate in the study&#xD;
&#xD;
          -  Pregnancy, nursing female subjects, or subjects trying to conceive, or not using&#xD;
             medically acceptable form of contraception&#xD;
&#xD;
          -  Asthma: Subjects who have a primary diagnosis of asthma (Note: Subjects with a prior&#xD;
             history of asthma are eligible if COPD is currently their primary diagnosis).&#xD;
&#xD;
          -  Alpha 1 Antitrypsin Deficiency: Subjects who have alpha 1 antitrypsin deficiency as&#xD;
             the cause of COPD -Active pulmonary disease such as active tuberculosis, lung cancer,&#xD;
             bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension,&#xD;
             interstitial lung disease, and uncontrolled sleep apnea (ie., in the opinion of the&#xD;
             Investigator severity of the disorder would impact the conduct of the study)-&#xD;
&#xD;
          -  Clinically significant neurologic, cardiovascular, hepatic, renal, endocrinologic,&#xD;
             pulmonary, hematological, psychiatric, or other medical illness that would interfere&#xD;
             with participation in this study&#xD;
&#xD;
          -  Poorly Controlled COPD&#xD;
&#xD;
          -  History of ECG abnormalities&#xD;
&#xD;
          -  Cancer not in complete remission for at least 5 years&#xD;
&#xD;
          -  Clinically significant, symptomatic prostatic hypertrophy&#xD;
&#xD;
          -  Male subjects with a trans-urethral resection of the prostate or full resection of the&#xD;
             prostate within 6 months prior to Screening&#xD;
&#xD;
          -  Clinically significant bladder neck obstruction or urinary retention&#xD;
&#xD;
          -  Inadequately treated glaucoma&#xD;
&#xD;
          -  History of an allergic reaction or hypersensitivity to any drug or to any component of&#xD;
             the formulations used in this study&#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>Shahid Siddiqui, MD, MHSA</last_name>
    <role>Study Director</role>
    <affiliation>Pearl Therapeutics, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Rolling Hills Estates</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Panama City</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Saint Charles</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Dublin</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&amp;studyid=4145&amp;filename=PT009001-Protocol_Redacted_11APR2018.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>July 16, 2014</study_first_submitted>
  <study_first_submitted_qc>July 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>December 20, 2016</results_first_submitted>
  <results_first_submitted_qc>March 29, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 9, 2017</results_first_posted>
  <disposition_first_submitted>February 16, 2016</disposition_first_submitted>
  <disposition_first_submitted_qc>February 16, 2016</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">March 16, 2016</disposition_first_posted>
  <last_update_submitted>May 23, 2018</last_update_submitted>
  <last_update_submitted_qc>May 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 20, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Budesonide and formoterol inhalation aerosol</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study was conducted at 20 sites in the United States from August 2014 to March 2015. Study participation was a maximum of 28 days.</recruitment_details>
      <pre_assignment_details>A Randomized, Double-Blind, Chronic Dosing (28 Days), Four-Period, Five-Treatment, Incomplete Block, Multi-Center, Crossover Study. Subjects completed final visit procedures. Final telephone follow-up occurred between 7 to 14 days from Visit 13. By-sequence tabulations of the data were not pre-specified.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Subjects</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="180"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BFF MDI 320/9.6 μg</title>
              <participants_list>
                <participants group_id="P1" count="155"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BFF MDI 160/9.6 μg</title>
              <participants_list>
                <participants group_id="P1" count="106"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BFF MDI 80/9.6 μg</title>
              <participants_list>
                <participants group_id="P1" count="103"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>BD MDI 320 μg</title>
              <participants_list>
                <participants group_id="P1" count="108"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>FF MDI 9.6 μg</title>
              <participants_list>
                <participants group_id="P1" count="157"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="133"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The ITT population used in participant flow, Population is defined as all subjects who were randomized to treatment and received at least one dose of BFF MDI 320/9.6 ug, BFF MDI 160/9.6 ug, BFF MDI 80/9.6 ug, BD MDI 320 ug or FF MDI 9.6 ug. Statistical tabulations and analyses will be by randomized treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Subjects</title>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="180"/>
          </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="62.2" spread="8.4"/>
                  </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="96"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>FEV1 AUC0-12 on Day 29</title>
        <description>Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)</description>
        <time_frame>Day 29</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 AUC0-12 on Day 29</title>
          <description>Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)</description>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
                <count group_id="O5" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.231" lower_limit="0.197" upper_limit="0.266"/>
                    <measurement group_id="O2" value="0.197" lower_limit="0.158" upper_limit="0.236"/>
                    <measurement group_id="O3" value="0.205" lower_limit="0.165" upper_limit="0.244"/>
                    <measurement group_id="O4" value="0.011" lower_limit="-0.028" upper_limit="0.050"/>
                    <measurement group_id="O5" value="0.176" lower_limit="0.141" upper_limit="0.210"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days</title>
        <time_frame>Over 28 days</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="97"/>
                <count group_id="O4" value="102"/>
                <count group_id="O5" value="147"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.138" lower_limit="0.111" upper_limit="0.165"/>
                    <measurement group_id="O2" value="0.121" lower_limit="0.089" upper_limit="0.153"/>
                    <measurement group_id="O3" value="0.110" lower_limit="0.078" upper_limit="0.142"/>
                    <measurement group_id="O4" value="0.022" lower_limit="-0.009" upper_limit="0.054"/>
                    <measurement group_id="O5" value="0.083" lower_limit="0.056" upper_limit="0.110"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change From Baseline in FEV1 (in Liters) Day 15</title>
        <time_frame>Day 15</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change From Baseline in FEV1 (in Liters) Day 15</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="97"/>
                <count group_id="O4" value="101"/>
                <count group_id="O5" value="146"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.388" lower_limit="0.354" upper_limit="0.422"/>
                    <measurement group_id="O2" value="0.366" lower_limit="0.327" upper_limit="0.405"/>
                    <measurement group_id="O3" value="0.348" lower_limit="0.308" upper_limit="0.387"/>
                    <measurement group_id="O4" value="0.143" lower_limit="0.104" upper_limit="0.182"/>
                    <measurement group_id="O5" value="0.320" lower_limit="0.286" upper_limit="0.354"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change From Baseline in FEV1 (in Liters) Day 29</title>
        <time_frame>Day 29</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change From Baseline in FEV1 (in Liters) Day 29</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
                <count group_id="O5" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.390" lower_limit="0.356" upper_limit="0.424"/>
                    <measurement group_id="O2" value="0.356" lower_limit="0.317" upper_limit="0.395"/>
                    <measurement group_id="O3" value="0.359" lower_limit="0.319" upper_limit="0.398"/>
                    <measurement group_id="O4" value="0.138" lower_limit="0.099" upper_limit="0.177"/>
                    <measurement group_id="O5" value="0.322" lower_limit="0.287" upper_limit="0.356"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change From Baseline in FEV1 on Day 1</title>
        <time_frame>Day 1</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change From Baseline in FEV1 on Day 1</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="151"/>
                <count group_id="O2" value="100"/>
                <count group_id="O3" value="97"/>
                <count group_id="O4" value="104"/>
                <count group_id="O5" value="148"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.338" lower_limit="0.304" upper_limit="0.372"/>
                    <measurement group_id="O2" value="0.310" lower_limit="0.271" upper_limit="0.349"/>
                    <measurement group_id="O3" value="0.314" lower_limit="0.275" upper_limit="0.354"/>
                    <measurement group_id="O4" value="0.096" lower_limit="0.058" upper_limit="0.135"/>
                    <measurement group_id="O5" value="0.313" lower_limit="0.279" upper_limit="0.347"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Forced Vital Capacity (FVC) AUC0-12 on Day 29</title>
        <time_frame>Day 29</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Vital Capacity (FVC) AUC0-12 on Day 29</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="148"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
                <count group_id="O5" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.305" lower_limit="0.244" upper_limit="0.365"/>
                    <measurement group_id="O2" value="0.245" lower_limit="0.176" upper_limit="0.315"/>
                    <measurement group_id="O3" value="0.267" lower_limit="0.196" upper_limit="0.337"/>
                    <measurement group_id="O4" value="0.002" lower_limit="-0.068" upper_limit="0.071"/>
                    <measurement group_id="O5" value="0.253" lower_limit="0.191" upper_limit="0.314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Transition Dyspnea Index (TDI) Focal Score on Day 29</title>
        <description>Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)</description>
        <time_frame>Day 29</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Transition Dyspnea Index (TDI) Focal Score on Day 29</title>
          <description>Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)</description>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods.</population>
          <units>Index</units>
          <param>Least Squares Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="149"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="100"/>
                <count group_id="O5" value="142"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.598" lower_limit="0.298" upper_limit="0.899"/>
                    <measurement group_id="O2" value="0.882" lower_limit="0.518" upper_limit="1.246"/>
                    <measurement group_id="O3" value="0.459" lower_limit="0.093" upper_limit="0.825"/>
                    <measurement group_id="O4" value="-0.109" lower_limit="-0.468" upper_limit="0.250"/>
                    <measurement group_id="O5" value="0.260" lower_limit="-0.047" upper_limit="0.566"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment</title>
        <time_frame>Visit 12-13 (7 days)</time_frame>
        <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
        <group_list>
          <group group_id="O1">
            <title>BFF MDI 320/9.6 ug</title>
            <description>BFF MDI 320/9.6 ug</description>
          </group>
          <group group_id="O2">
            <title>BFF MDI 160/9.6 ug</title>
            <description>BFF MDI 160/9.6 ug</description>
          </group>
          <group group_id="O3">
            <title>BFF MDI 80/9.6 ug</title>
            <description>BFF MDI 80/9.6 ug</description>
          </group>
          <group group_id="O4">
            <title>BD MDI 320 ug</title>
            <description>BD MDI 320 ug</description>
          </group>
          <group group_id="O5">
            <title>FF MDI 9.6 ug</title>
            <description>FF MDI 9.6 ug</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment</title>
          <population>MITT Population is a subset of the ITT population which includes subjects who received treatment and had post-treatment efficacy data from at least two Treatment Periods</population>
          <units>Puffs</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="152"/>
                <count group_id="O2" value="101"/>
                <count group_id="O3" value="98"/>
                <count group_id="O4" value="104"/>
                <count group_id="O5" value="149"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.05" lower_limit="-0.34" upper_limit="0.43"/>
                    <measurement group_id="O2" value="0.16" lower_limit="-0.27" upper_limit="0.58"/>
                    <measurement group_id="O3" value="0.24" lower_limit="-0.19" upper_limit="0.67"/>
                    <measurement group_id="O4" value="0.96" lower_limit="0.54" upper_limit="1.38"/>
                    <measurement group_id="O5" value="0.44" lower_limit="0.06" upper_limit="0.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs were recorded from the time subjects received their first dose of study medication, during the entire study period, and up to 14 days from the date of the last study medication dose.</time_frame>
      <desc>The Safety population was defined as all subjects who were randomized to treatment and received at least 1 dose of the study treatment. Subjects in the Safety population were analyzed according to the treatment received.</desc>
      <group_list>
        <group group_id="E1">
          <title>BFF MDI 320/9.6 ug</title>
          <description>BFF MDI 320/9.6 ug</description>
        </group>
        <group group_id="E2">
          <title>BFF MDI 160/9.6 ug</title>
          <description>BFF MDI 160/9.6 ug</description>
        </group>
        <group group_id="E3">
          <title>BFF MDI 80/9.6 ug</title>
          <description>BFF MDI 80/9.6 ug</description>
        </group>
        <group group_id="E4">
          <title>BD MDI 320 ug</title>
          <description>BD MDI 320 ug</description>
        </group>
        <group group_id="E5">
          <title>FF MDI 9.6 ug</title>
          <description>FF MDI 9.6 ug</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, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="103"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="108"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small Intestinal Obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Clostridium Difficile Colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Prostate Cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular Accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic Obstructive Pulmonary Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Laryngeal Oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>2</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="12" subjects_at_risk="155"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="106"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="103"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="108"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="155"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="155"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="106"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="103"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="108"/>
                <counts group_id="E5" events="5" subjects_affected="5" subjects_at_risk="157"/>
              </event>
              <event>
                <sub_title>Upper Respiratory Tract Infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="108"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="157"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="155"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="106"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="103"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="108"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="157"/>
              </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 of this study must be submitted at least 30 days prior to submission for publication or presentation to Pearl Therapeutics for review, approval, and to ensure consistency. Pearl Therapeutics has 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>Paul Dorinsky, MD, FCCP</name_or_title>
      <organization>Pearl Therapeutics Inc.</organization>
      <phone>650-305-2600</phone>
      <email>pdorinsky@pearltherapeutics.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/NCT02196077
org study id: PT009001
nct id: NCT02196077
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase IIb, randomized, double blind, chronic dosing (28 days), four period, five
      treatment, incomplete block, crossover design in subjects with moderate to severe COPD. The
      overall objective is to demonstrate that the combination of budesonide (BD; PT008) and
      formoterol fumarate (FF; PT005) in a metered-dose inhaler (MDI); (BFF MDI; PT009) provides
      benefit on lung function compared with BD MDI in subjects with moderate to severe COPD.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: Double Blind
measure: FEV1 AUC0-12 on Day 29
time frame: Day 29
description: Change from Baseline in forced expiratory volume in 1 second (FEV1) area under the curve from 0 to 12 hours (AUC0-12)
measure: Change From Baseline in Morning Pre-dose Trough FEV1 Over 28 Days
time frame: Over 28 days
measure: Peak Change From Baseline in FEV1 (in Liters) Day 15
time frame: Day 15
measure: Peak Change From Baseline in FEV1 (in Liters) Day 29
time frame: Day 29
measure: Peak Change From Baseline in FEV1 on Day 1
time frame: Day 1
measure: Forced Vital Capacity (FVC) AUC0-12 on Day 29
time frame: Day 29
measure: Transition Dyspnea Index (TDI) Focal Score on Day 29
time frame: Day 29
description: Min/Max Range of TDI scale -9 (major deterioration) to +9 (major improvement)
measure: Change From Baseline in Average Daily Use of Rescue Ventolin HFA Over the Last Week of Treatment
time frame: Visit 12-13 (7 days)
arm group label: BFF MDI 320/9.6 μg
arm group type: Experimental
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BFF MDI 160/9.6 μg
arm group type: Experimental
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI)160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BFF MDI 80/9.6 μg
arm group type: Experimental
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BD MDI 320 μg
arm group type: Experimental
description: Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)
arm group label: FF MDI 9.6 μg
arm group type: Experimental
description: Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)
intervention type: Drug
intervention name: BFF MDI 320/9.6 μg
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 320/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BFF MDI 320/9.6 μg
intervention type: Drug
intervention name: BFF MDI 160/9.6 μg
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 160/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BFF MDI 160/9.6 μg
intervention type: Drug
intervention name: BFF MDI 80/9.6 μg
description: Budesonide and formoterol fumarate metered dose inhaler (BFF MDI) 80/9.6 μg; PT009 administered as 2 inhalations, twice daily (BID)
arm group label: BFF MDI 80/9.6 μg
intervention type: Drug
intervention name: BD MDI 320 μg
description: Budesonide metered dose inhaler (BD MDI) 320 μg; PT008 administered as 2 inhalations, twice daily (BID)
arm group label: BD MDI 320 μg
intervention type: Drug
intervention name: FF MDI 9.6 μg
description: Formoterol fumarate metered dose inhaler (FF MDI) 9.6 μg; PT005 administered as 2 inhalations, twice daily (BID)
arm group label: FF MDI 9.6 μg
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Shahid Siddiqui, MD, MHSA
role: Study Director
affiliation: Pearl Therapeutics, Inc.
facility: 
facility: 
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country: United States
url: http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=4145&filename=PT009001-Protocol_Redacted_11APR2018.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: Yes
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 