<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/NCT03256552</url>
  </required_header>
  <id_info>
    <org_study_id>PT001004</org_study_id>
    <nct_id>NCT03256552</nct_id>
  </id_info>
  <brief_title>Study to Assess the Efficacy and Safety of Three Doses of PT001 in Japanese Subjects With Moderate to Severe COPD</brief_title>
  <official_title>A Randomized, Double-Blind, Chronic Dosing (7-Day), Four-Period, Four-Treatment, Placebo-Controlled, Cross-Over, Multi-Center Study to Assess the Efficacy and Safety of Three Doses of PT001 in Japanese 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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The overall objective of this study was to assess the efficacy and safety of GP MDI relative&#xD;
      to placebo in Japanese subjects with moderate to severe COPD. Each subject received the 4&#xD;
      separate study treatments, scheduled as four, 7-day, treatment periods for a total treatment&#xD;
      duration of 28 days.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment,&#xD;
      placebo-controlled, crossover, multi-center study to assess the efficacy and safety of 3&#xD;
      doses of GP MDI (28.8, 14.4, and 7.2 μg ex-actuator, BID) in Japanese subjects with moderate&#xD;
      to severe COPD.&#xD;
&#xD;
      Subjects who met the entry criteria had their maintenance therapy for COPD adjusted, as&#xD;
      specified in the protocol. To allow for an adequate washout of previous maintenance&#xD;
      medications, subjects underwent a washout period of at least 7 days, but not greater than 28&#xD;
      days duration prior to returning to the clinic for Visit 2 (Randomization Visit; Day 1 of&#xD;
      Treatment Period 1).&#xD;
&#xD;
      The 4 study treatments were GP MDI 28.8, 14.4, and 7.2 μg ex-actuator, and Placebo MDI BID.&#xD;
      Subjects were randomly assigned to 1 of the following 4 treatment sequences (ABCD, BDAC,&#xD;
      CADB, DCBA) in a 1:1:1:1 ratio using an Interactive Web Response System where each letter&#xD;
      represented 1 of the 4 treatments included in the study by random assignment.&#xD;
&#xD;
      Subjects were to complete 7 days of dosing in each of the 4 Treatment Periods, with each&#xD;
      Treatment Period separated by a washout period of 5 to 21 days.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 28, 2015</start_date>
  <completion_date type="Actual">September 5, 2015</completion_date>
  <primary_completion_date type="Actual">September 5, 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>
    <intervention_model_description>randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Morning Pre-dose Trough FEV1</measure>
    <time_frame>Baseline, Day 8</time_frame>
    <description>Change from Baseline in Morning Pre-dose Trough FEV1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FEV1 AUC0-2</measure>
    <time_frame>Day 1 and Day 8</time_frame>
    <description>Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Change in FEV1</measure>
    <time_frame>Day 1 and Day 8</time_frame>
    <description>Peak Change from Baseline in FEV1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC AUC0-2</measure>
    <time_frame>Baseline, Day 8</time_frame>
    <description>Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>GP MDI 28.8 micrograms</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Glycopyrronium Metered Dose Inhaler 28.8 micrograms</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GP MDI 14.4 micrograms</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Glycopyrronium Metered Dose Inhaler 14.4 micrograms</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GP MDI 7.2 micrograms</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Glycopyrronium Metered Dose Inhaler 7.2 micrograms</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo MDI</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo Inhalation Aerosol</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrronium MDI 28.8 micrograms</intervention_name>
    <description>Glycopyrronium MDI 28.8 micrograms</description>
    <arm_group_label>GP MDI 28.8 micrograms</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrronium MDI 14.4 micrograms</intervention_name>
    <description>Glycopyrronium MDI 14.4 micrograms</description>
    <arm_group_label>GP MDI 14.4 micrograms</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrronium MDI 7.2 micrograms</intervention_name>
    <description>Glycopyrronium MDI 7.2 micrograms</description>
    <arm_group_label>GP MDI 7.2 micrograms</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo MDI</intervention_name>
    <description>Placebo Inhalation Aerosol</description>
    <arm_group_label>Placebo MDI</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical history of COPD with a moderate to severe classification&#xD;
&#xD;
          -  Current and former smokers with a history of at least 10 pack-years of cigarette&#xD;
             smoking.&#xD;
&#xD;
        -Post-bronchodilator FEV1 must be ≥30% and &lt;80% predicted normal value-&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Primary asthma diagnosis; Poorly controlled COPD defined as acute worsening of COPD&#xD;
             that required treatment with corticosteroids or antibiotics in the 6-week interval&#xD;
             prior to Screening or between Screening and Visit 2;&#xD;
&#xD;
          -  Clinically significant abnormal ECG&#xD;
&#xD;
          -  Other 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; Cancer that was not in&#xD;
             complete remission for at least 5 years;&#xD;
&#xD;
          -  Diagnosis of angle closure glaucoma&#xD;
&#xD;
          -  A documented myocardial infarction within 1 year of Screening.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Fukuoka-shi</city>
        <state>Fukuoka-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Iizuka-shi</city>
        <state>Fukuoka-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Mizunami-shi</city>
        <state>Gifu-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Sapporo-shi</city>
        <state>Hokkaido</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Ako-shi</city>
        <state>Hyogo-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kakogawa-shi</city>
        <state>Hyogo-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kobe-Shi</city>
        <state>Hyogo-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Nishinomiya-shi</city>
        <state>Hyogo-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Himeji-shi</city>
        <state>Hyogo</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Naka-gun</city>
        <state>Ibaraki-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kawasaki-shi</city>
        <state>Kanagawa-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kyoto-shi</city>
        <state>Kyoto-Fu</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kasaoka-shi</city>
        <state>Okayama-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Kishiwada-shi</city>
        <state>Osaka-Fu</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Osaka-shi</city>
        <state>Osaka-Fu</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Hamamatsu-shi</city>
        <state>Shizuoka-Ken</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Chuo-ku</city>
        <state>Tokyo-To</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pearl Investigative Site</name>
      <address>
        <city>Toshima-ku</city>
        <state>Tokyo-To</state>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 22, 2017</study_first_posted>
  <results_first_submitted>November 13, 2017</results_first_submitted>
  <results_first_submitted_qc>December 22, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">January 23, 2018</results_first_posted>
  <last_update_submitted>December 22, 2017</last_update_submitted>
  <last_update_submitted_qc>December 22, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">January 23, 2018</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>Glycopyrrolate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Conducted at 20 sites in Japan from January-September 2015. Entire period of study participation per subject was a maximum of 19 weeks. Planned target enrollment of 60 subjects.</recruitment_details>
      <pre_assignment_details>This was a chronic dosing (7 days), 4-period, 4-treatment, placebo-controlled, crossover study. Each subject was randomized to 1 of 4 sequences. Each sequence included the four treatment groups. By-treatment sequence tabulations of the data were not pre-specified.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Overall Study</title>
          <description>All Subjects Randomized</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="66"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>GP MDI 28.8 µg</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>GP MDI 14.4 µg</title>
              <participants_list>
                <participants group_id="P1" count="63"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>GP MDI 7.2 µg</title>
              <participants_list>
                <participants group_id="P1" count="62"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo MDI</title>
              <participants_list>
                <participants group_id="P1" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="61"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </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>Adverse Event</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="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.</population>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>All Subjects in the MITT Population</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="62"/>
          </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="67.5" spread="7.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Morning Pre-dose Trough FEV1</title>
        <description>Change from Baseline in Morning Pre-dose Trough FEV1</description>
        <time_frame>Baseline, Day 8</time_frame>
        <population>MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.</population>
        <group_list>
          <group group_id="O1">
            <title>GP MDI 28.8 µg</title>
            <description>Glycopyrronium MDI 28.8 µg</description>
          </group>
          <group group_id="O2">
            <title>GP MDI 14.4 µg</title>
            <description>Glycopyrronium 14.4 µg</description>
          </group>
          <group group_id="O3">
            <title>GP MDI 7.2 µg</title>
            <description>Glycopyrronium 7.2 µg</description>
          </group>
          <group group_id="O4">
            <title>Placebo MDI</title>
            <description>Placebo MDI</description>
          </group>
        </group_list>
        <measure>
          <title>Morning Pre-dose Trough FEV1</title>
          <description>Change from Baseline in Morning Pre-dose Trough FEV1</description>
          <population>MITT Population defined as all 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="61"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.101" lower_limit="0.068" upper_limit="0.134"/>
                    <measurement group_id="O2" value="0.098" lower_limit="0.066" upper_limit="0.131"/>
                    <measurement group_id="O3" value="0.077" lower_limit="0.045" upper_limit="0.110"/>
                    <measurement group_id="O4" value="-0.031" lower_limit="-0.064" upper_limit="0.002"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FEV1 AUC0-2</title>
        <description>Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
        <time_frame>Day 1 and Day 8</time_frame>
        <population>MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.</population>
        <group_list>
          <group group_id="O1">
            <title>GP MDI 28.8 µg</title>
            <description>Glycopyrronium MDI 28.8 µg</description>
          </group>
          <group group_id="O2">
            <title>GP MDI 14.4 µg</title>
            <description>Glycopyrronium 14.4 µg</description>
          </group>
          <group group_id="O3">
            <title>GP MDI 7.2 µg</title>
            <description>Glycopyrronium 7.2 µg</description>
          </group>
          <group group_id="O4">
            <title>Placebo MDI</title>
            <description>Placebo MDI</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 AUC0-2</title>
          <description>Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
          <population>MITT Population defined as all 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="61"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.176" lower_limit="0.146" upper_limit="0.205"/>
                    <measurement group_id="O2" value="0.140" lower_limit="0.111" upper_limit="0.170"/>
                    <measurement group_id="O3" value="0.127" lower_limit="0.098" upper_limit="0.157"/>
                    <measurement group_id="O4" value="0.043" lower_limit="0.014" upper_limit="0.073"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.194" lower_limit="0.157" upper_limit="0.230"/>
                    <measurement group_id="O2" value="0.199" lower_limit="0.162" upper_limit="0.236"/>
                    <measurement group_id="O3" value="0.170" lower_limit="0.133" upper_limit="0.206"/>
                    <measurement group_id="O4" value="0.019" lower_limit="-0.018" upper_limit="0.055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Change in FEV1</title>
        <description>Peak Change from Baseline in FEV1</description>
        <time_frame>Day 1 and Day 8</time_frame>
        <population>MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.</population>
        <group_list>
          <group group_id="O1">
            <title>GP MDI 28.8 µg</title>
            <description>Glycopyrronium MDI 28.8 µg</description>
          </group>
          <group group_id="O2">
            <title>GP MDI 14.4 µg</title>
            <description>Glycopyrronium 14.4 µg</description>
          </group>
          <group group_id="O3">
            <title>GP MDI 7.2 µg</title>
            <description>Glycopyrronium 7.2 µg</description>
          </group>
          <group group_id="O4">
            <title>Placebo MDI</title>
            <description>Placebo MDI</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Change in FEV1</title>
          <description>Peak Change from Baseline in FEV1</description>
          <population>MITT Population defined as all 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="61"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="62"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.254" lower_limit="0.219" upper_limit="0.289"/>
                    <measurement group_id="O2" value="0.212" lower_limit="0.177" upper_limit="0.247"/>
                    <measurement group_id="O3" value="0.192" lower_limit="0.157" upper_limit="0.227"/>
                    <measurement group_id="O4" value="0.104" lower_limit="0.069" upper_limit="0.139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.260" lower_limit="0.219" upper_limit="0.301"/>
                    <measurement group_id="O2" value="0.265" lower_limit="0.224" upper_limit="0.306"/>
                    <measurement group_id="O3" value="0.238" lower_limit="0.197" upper_limit="0.279"/>
                    <measurement group_id="O4" value="0.082" lower_limit="0.041" upper_limit="0.124"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FVC AUC0-2</title>
        <description>Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
        <time_frame>Baseline, Day 8</time_frame>
        <population>MITT Population defined as all subjects who received treatment and had post-treatment efficacy data from at least two treatment periods.</population>
        <group_list>
          <group group_id="O1">
            <title>GP MDI 28.8 µg</title>
            <description>Glycopyrronium MDI 28.8 µg</description>
          </group>
          <group group_id="O2">
            <title>GP MDI 14.4 µg</title>
            <description>Glycopyrronium 14.4 µg</description>
          </group>
          <group group_id="O3">
            <title>GP MDI 7.2 µg</title>
            <description>Glycopyrronium 7.2 µg</description>
          </group>
          <group group_id="O4">
            <title>Placebo MDI</title>
            <description>Placebo MDI</description>
          </group>
        </group_list>
        <measure>
          <title>FVC AUC0-2</title>
          <description>Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.</description>
          <population>MITT Population defined as all 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="61"/>
                <count group_id="O2" value="61"/>
                <count group_id="O3" value="62"/>
                <count group_id="O4" value="61"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.273" lower_limit="0.207" upper_limit="0.339"/>
                    <measurement group_id="O2" value="0.265" lower_limit="0.199" upper_limit="0.331"/>
                    <measurement group_id="O3" value="0.223" lower_limit="0.157" upper_limit="0.288"/>
                    <measurement group_id="O4" value="0.047" lower_limit="-0.019" upper_limit="0.113"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected from the time the subject signed consent up to the follow-up visit 7-14 days after last dose of study drug.</time_frame>
      <desc>Safety population included all participants who received at least one dose of investigational drug and had safety data available; participants were included in safety population according to the investigational drug received</desc>
      <group_list>
        <group group_id="E1">
          <title>GP MDI 28.8 µg</title>
          <description>Glycopyrronium MDI 28.8 µg</description>
        </group>
        <group group_id="E2">
          <title>GP MDI 14.4 µg</title>
          <description>Glycopyrronium 14.4 µg</description>
        </group>
        <group group_id="E3">
          <title>GP MDI 7.2 µg</title>
          <description>Glycopyrronium 7.2 µg</description>
        </group>
        <group group_id="E4">
          <title>Placebo MDI</title>
          <description>Placebo MDI</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="0" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </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="0" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</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="2" subjects_at_risk="61"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="61"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="63"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="62"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="65"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="61"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="63"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="62"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="65"/>
              </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>Colin Reisner, MD, FCCP, FAAAAI</name_or_title>
      <organization>Pearl Therapeutics, Inc</organization>
      <phone>650-305-2600</phone>
      <email>creisner@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/NCT03256552
org study id: PT001004
nct id: NCT03256552
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The overall objective of this study was to assess the efficacy and safety of GP MDI relative
      to placebo in Japanese subjects with moderate to severe COPD. Each subject received the 4
      separate study treatments, scheduled as four, 7-day, treatment periods for a total treatment
      duration of 28 days.
This was a randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment,
      placebo-controlled, crossover, multi-center study to assess the efficacy and safety of 3
      doses of GP MDI (28.8, 14.4, and 7.2 μg ex-actuator, BID) in Japanese subjects with moderate
      to severe COPD.

      Subjects who met the entry criteria had their maintenance therapy for COPD adjusted, as
      specified in the protocol. To allow for an adequate washout of previous maintenance
      medications, subjects underwent a washout period of at least 7 days, but not greater than 28
      days duration prior to returning to the clinic for Visit 2 (Randomization Visit; Day 1 of
      Treatment Period 1).

      The 4 study treatments were GP MDI 28.8, 14.4, and 7.2 μg ex-actuator, and Placebo MDI BID.
      Subjects were randomly assigned to 1 of the following 4 treatment sequences (ABCD, BDAC,
      CADB, DCBA) in a 1:1:1:1 ratio using an Interactive Web Response System where each letter
      represented 1 of the 4 treatments included in the study by random assignment.

      Subjects were to complete 7 days of dosing in each of the 4 Treatment Periods, with each
      Treatment Period separated by a washout period of 5 to 21 days.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: randomized, double-blind, chronic-dosing (7-day), four-period, four-treatment, placebo-controlled, crossover, multi-center
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Morning Pre-dose Trough FEV1
time frame: Baseline, Day 8
description: Change from Baseline in Morning Pre-dose Trough FEV1
measure: FEV1 AUC0-2
time frame: Day 1 and Day 8
description: Change from Baseline in FEV1 AUC0-2 normalized for length of follow-up. FEV1 was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.
measure: Peak Change in FEV1
time frame: Day 1 and Day 8
description: Peak Change from Baseline in FEV1
measure: FVC AUC0-2
time frame: Baseline, Day 8
description: Change from Baseline in FVC AUC0-2 on Day 8 normalized for length of follow-up. FVC was measured at 15 min, 30 min, 1 hour, and 2 hours post dose.
arm group label: GP MDI 28.8 micrograms
arm group type: Active Comparator
description: Glycopyrronium Metered Dose Inhaler 28.8 micrograms
arm group label: GP MDI 14.4 micrograms
arm group type: Active Comparator
description: Glycopyrronium Metered Dose Inhaler 14.4 micrograms
arm group label: GP MDI 7.2 micrograms
arm group type: Active Comparator
description: Glycopyrronium Metered Dose Inhaler 7.2 micrograms
arm group label: Placebo MDI
arm group type: Placebo Comparator
description: Placebo Inhalation Aerosol
intervention type: Drug
intervention name: Glycopyrronium MDI 28.8 micrograms
description: Glycopyrronium MDI 28.8 micrograms
arm group label: GP MDI 28.8 micrograms
intervention type: Drug
intervention name: Glycopyrronium MDI 14.4 micrograms
description: Glycopyrronium MDI 14.4 micrograms
arm group label: GP MDI 14.4 micrograms
intervention type: Drug
intervention name: Glycopyrronium MDI 7.2 micrograms
description: Glycopyrronium MDI 7.2 micrograms
arm group label: GP MDI 7.2 micrograms
intervention type: Drug
intervention name: Placebo MDI
description: Placebo Inhalation Aerosol
arm group label: Placebo MDI
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 