<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/NCT01699685</url>
  </required_header>
  <id_info>
    <org_study_id>CNVA237ACH01</org_study_id>
    <secondary_id>2012-002362-13</secondary_id>
    <nct_id>NCT01699685</nct_id>
  </id_info>
  <brief_title>Swiss studY for the Treatment of COPD Patients With the Free combiNation of indacatERol and GlYcopyrroniumbromide.</brief_title>
  <acronym>SYNERGY</acronym>
  <official_title>A Multicenter, Randomized, Double-blind, Single-dose Study to Assess the Effect of the QAB149 and NVA237 Combination Versus QAB149 Alone on Inspiratory Capacity in Patients With Moderate or Severe COPD.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study purpose is to evaluate the effect of QAB149&#xD;
&#xD;
        -  NVA237 vs. QAB149 on static lung hyperinflation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter, randomized, double-blinded, single-dose, cross-over,&#xD;
      placebo-controlled study. The primary endpoint was chosen to demonstrate the superiority of a&#xD;
      single-dose of the combined inhalation vs. the mono inhalation regarding the Inspiratory&#xD;
      Capacity (IC) peak value. A total of 78 patients will be randomized to complete two visits&#xD;
      with two single doses of treatment. Patients will be randomized in a cross-over manner.&#xD;
      Treatment visits will be separated by a study medication wash-out period.Treatments will be&#xD;
      administered in a blinded fashion.&#xD;
&#xD;
      The patients will be male and female patients, ≥40 years of age, with a documented diagnosis&#xD;
      of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung&#xD;
      Disease (GOLD) criteria and &gt;10-pack years history of smoking, FEV1 &lt;80% and ≥30% of the&#xD;
      predicted normal value.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 3</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>
  </study_design_info>
  <primary_outcome>
    <measure>Inspiratory Capacity (IC) Peak Value</measure>
    <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
    <description>IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Forced Expiratory Volume in One Second (FEV1)</measure>
    <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
    <description>FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inspiratory Capacity (IC)</measure>
    <time_frame>within 4h after dosing</time_frame>
    <description>During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced Volume Capacity (FVC)</measure>
    <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
    <description>FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Lung Capacity (TLC)</measure>
    <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
    <description>TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Airway Resistance (Raw)</measure>
    <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
    <description>Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease: COPD</condition>
  <arm_group>
    <arm_group_label>Sequence A</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patients will inhale QAB149 (capsule form in blister packs) + Placebo via Novartis Concept 1 SDDPI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sequence B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will inhale QAB149 plus NVA237 (capsule form in blister packs) via Novartis Concept 1 SDDPI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QAB149</intervention_name>
    <description>Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI</description>
    <arm_group_label>Sequence A</arm_group_label>
    <arm_group_label>Sequence B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI</description>
    <arm_group_label>Sequence A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVA237</intervention_name>
    <description>Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI</description>
    <arm_group_label>Sequence B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Male and female patients, ≥40 years of age, with a documented diagnosis of moderate or&#xD;
             severe COPD according to Global Initiative for Chronic Obstructive Lung Disease (GOLD)&#xD;
             criteria and &gt;10-pack year history of smoking&#xD;
&#xD;
          -  FEV1 &lt;80% and ≥30% of the predicted normal value who have signed an informed consent&#xD;
             form prior to the initiation of any study-related procedure&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  No COPD exacerbations within 6 weeks prior to dosing&#xD;
&#xD;
          -  No concomitant lung disease such as asthma&#xD;
&#xD;
          -  Nno requirement for long term oxygen treatment or history of lung reduction surgery&#xD;
&#xD;
          -  No medical conditions that would interfere with the performance of spirometry&#xD;
&#xD;
          -  No other medical condition that in the opinion of the investigator may cause the&#xD;
             patient to be unsuitable for completion of the study or place the patient at potential&#xD;
             risk form being in the study e.g. uncontrolled hypertension or unstable ischemic heart&#xD;
             disease.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Corinne Wild, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Corinne Wild, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Martin Brutsche, Prof. Dr. med.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kantonsspital St. Gallen, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Faltigberg-Wald</city>
        <state>ZH</state>
        <zip>8639</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barmelweid</city>
        <zip>5017</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Basel</city>
        <zip>4031</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bern</city>
        <zip>3010</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bern</city>
        <zip>3013</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Crans-Montana</city>
        <zip>3963</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lausanne</city>
        <zip>1011</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Locarno</city>
        <zip>6600</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lugano</city>
        <zip>6900</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Gallen</city>
        <zip>9007</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Walenstadtberg</city>
        <zip>8881</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>January 2016</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>October 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <results_first_submitted>June 26, 2015</results_first_submitted>
  <results_first_submitted_qc>January 11, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 9, 2016</results_first_posted>
  <last_update_submitted>January 11, 2016</last_update_submitted>
  <last_update_submitted_qc>January 11, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 9, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Moderate to severe COPD patients are included</keyword>
  <keyword>NVA</keyword>
  <keyword>QAB</keyword>
  <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>
      <group_list>
        <group group_id="P1">
          <title>Sequence A</title>
          <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
        </group>
        <group group_id="P2">
          <title>Sequence B</title>
          <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Population</title>
              <participants_list>
                <participants group_id="P1" count="39"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Population (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="38"/>
                <participants group_id="P2" count="38"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Medical or ethical, noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient request</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="36"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Demographic summary by treatment group (safety population, N = 77)</population>
      <group_list>
        <group group_id="B1">
          <title>Sequence A</title>
          <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
        </group>
        <group group_id="B2">
          <title>Sequence B</title>
          <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="39"/>
            <count group_id="B2" value="38"/>
            <count group_id="B3" value="77"/>
          </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="65.62" spread="9.247"/>
                    <measurement group_id="B2" value="64.18" spread="7.447"/>
                    <measurement group_id="B3" value="64.91" spread="8.383"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Inspiratory Capacity (IC) Peak Value</title>
        <description>IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).</description>
        <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Inspiratory Capacity (IC) Peak Value</title>
          <description>IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 0 (n=38, 38)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.87" spread="0.808"/>
                    <measurement group_id="O2" value="2.94" spread="0.777"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 6 (n=36, 36)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.99" spread="0.856"/>
                    <measurement group_id="O2" value="2.85" spread="0.707"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Forced Expiratory Volume in One Second (FEV1)</title>
        <description>FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations</description>
        <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Expiratory Volume in One Second (FEV1)</title>
          <description>FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day (0) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.49" spread="0.442"/>
                    <measurement group_id="O2" value="1.57" spread="0.505"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" spread="0.440"/>
                    <measurement group_id="O2" value="1.60" spread="0.506"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.51" spread="0.437"/>
                    <measurement group_id="O2" value="1.60" spread="0.506"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.53" spread="0.430"/>
                    <measurement group_id="O2" value="1.59" spread="0.500"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.53" spread="0.434"/>
                    <measurement group_id="O2" value="1.60" spread="0.492"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.59" spread="0.437"/>
                    <measurement group_id="O2" value="1.52" spread="0.473"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.63" spread="0.465"/>
                    <measurement group_id="O2" value="1.53" spread="0.463"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.66" spread="0.462"/>
                    <measurement group_id="O2" value="1.55" spread="0.476"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.65" spread="0.455"/>
                    <measurement group_id="O2" value="1.56" spread="0.470"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.64" spread="0.473"/>
                    <measurement group_id="O2" value="1.56" spread="0.459"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Inspiratory Capacity (IC)</title>
        <description>During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose</description>
        <time_frame>within 4h after dosing</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Inspiratory Capacity (IC)</title>
          <description>During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day (0) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.67" spread="0.771"/>
                    <measurement group_id="O2" value="2.75" spread="0.751"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.67" spread="0.799"/>
                    <measurement group_id="O2" value="2.79" spread="0.774"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.69" spread="0.803"/>
                    <measurement group_id="O2" value="2.71" spread="0.709"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" spread="0.811"/>
                    <measurement group_id="O2" value="2.69" spread="0.800"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.74" spread="0.823"/>
                    <measurement group_id="O2" value="2.74" spread="0.754"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.79" spread="0.826"/>
                    <measurement group_id="O2" value="2.40" spread="0.724"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.80" spread="0.810"/>
                    <measurement group_id="O2" value="2.72" spread="0.759"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.86" spread="0.846"/>
                    <measurement group_id="O2" value="2.74" spread="0.689"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.83" spread="0.841"/>
                    <measurement group_id="O2" value="2.69" spread="0.719"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.85" spread="0.799"/>
                    <measurement group_id="O2" value="2.68" spread="0.699"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Forced Volume Capacity (FVC)</title>
        <description>FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time</description>
        <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Volume Capacity (FVC)</title>
          <description>FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day (0) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.98" spread="0.917"/>
                    <measurement group_id="O2" value="3.00" spread="0.839"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.00" spread="0.966"/>
                    <measurement group_id="O2" value="3.02" spread="0.846"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.01" spread="0.947"/>
                    <measurement group_id="O2" value="3.04" spread="0.862"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.08" spread="0.946"/>
                    <measurement group_id="O2" value="3.04" spread="0.872"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.07" spread="0.968"/>
                    <measurement group_id="O2" value="3.07" spread="0.852"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.19" spread="1.002"/>
                    <measurement group_id="O2" value="2.96" spread="0.788"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.25" spread="1.047"/>
                    <measurement group_id="O2" value="2.97" spread="0.807"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.29" spread="1.018"/>
                    <measurement group_id="O2" value="2.99" spread="0.754"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.32" spread="1.003"/>
                    <measurement group_id="O2" value="2.98" spread="0.794"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.30" spread="1.012"/>
                    <measurement group_id="O2" value="2.96" spread="0.797"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Lung Capacity (TLC)</title>
        <description>TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose</description>
        <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Total Lung Capacity (TLC)</title>
          <description>TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day (0) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.20" spread="1.587"/>
                    <measurement group_id="O2" value="6.81" spread="1.144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.17" spread="1.559"/>
                    <measurement group_id="O2" value="6.79" spread="1.197"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.06" spread="1.658"/>
                    <measurement group_id="O2" value="6.81" spread="1.190"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.14" spread="1.662"/>
                    <measurement group_id="O2" value="6.82" spread="1.198"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.21" spread="1.608"/>
                    <measurement group_id="O2" value="6.78" spread="1.247"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.20" spread="1.664"/>
                    <measurement group_id="O2" value="6.79" spread="1.243"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.12" spread="1.576"/>
                    <measurement group_id="O2" value="6.80" spread="1.312"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.21" spread="1.641"/>
                    <measurement group_id="O2" value="6.80" spread="1.213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.23" spread="1.561"/>
                    <measurement group_id="O2" value="6.81" spread="1.304"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.30" spread="1.691"/>
                    <measurement group_id="O2" value="6.93" spread="1.376"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Airway Resistance (Raw)</title>
        <description>Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes</description>
        <time_frame>Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours</time_frame>
        <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Sequence A</title>
            <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
          </group>
          <group group_id="O2">
            <title>Sequence B</title>
            <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
          </group>
        </group_list>
        <measure>
          <title>Airway Resistance (Raw)</title>
          <description>Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes</description>
          <population>Full analysis set (FAS) included all randomized patients who received at least one dose of study medication during at least one study period. Participants with observations after 4 hours were included in the analysis</population>
          <units>cmH2O/l/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="38"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day (0) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.13" spread="2.243"/>
                    <measurement group_id="O2" value="4.74" spread="1.810"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.19" spread="2.561"/>
                    <measurement group_id="O2" value="4.61" spread="1.881"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.21" spread="2.496"/>
                    <measurement group_id="O2" value="4.43" spread="1.849"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.07" spread="2.528"/>
                    <measurement group_id="O2" value="4.53" spread="1.748"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (0) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.18" spread="2.535"/>
                    <measurement group_id="O2" value="4.48" spread="1.866"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 30 min post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.73" spread="2.540"/>
                    <measurement group_id="O2" value="5.18" spread="2.130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 1 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.47" spread="2.323"/>
                    <measurement group_id="O2" value="4.97" spread="1.861"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 2 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.31" spread="2.119"/>
                    <measurement group_id="O2" value="4.71" spread="1.822"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 3 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.30" spread="2.161"/>
                    <measurement group_id="O2" value="4.77" spread="1.989"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day (6) 4 hour post-dose</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.30" spread="2.170"/>
                    <measurement group_id="O2" value="4.78" spread="1.939"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Sequence A</title>
          <description>QAB149 (150μg puff) + placebo followed by QAB149 (150μg puff) + NVA237 (50μg puff)</description>
        </group>
        <group group_id="E2">
          <title>Sequence B</title>
          <description>QAB149 (150μg puff) + NVA237 (50μg puff) followed by QAB149 (150μg puff) + placebo</description>
        </group>
      </group_list>
      <serious_events>
        <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="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </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="5" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Forced expiratory volume decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Inspiratory capacity decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </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" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="38"/>
              </event>
              <event>
                <sub_title>Lung disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="38"/>
              </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>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
    </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/NCT01699685
org study id: CNVA237ACH01
secondary id: 2012-002362-13
nct id: NCT01699685
lead sponsor: 
has dmc: No
The study purpose is to evaluate the effect of QAB149

        -  NVA237 vs. QAB149 on static lung hyperinflation.
This is a multicenter, randomized, double-blinded, single-dose, cross-over,
      placebo-controlled study. The primary endpoint was chosen to demonstrate the superiority of a
      single-dose of the combined inhalation vs. the mono inhalation regarding the Inspiratory
      Capacity (IC) peak value. A total of 78 patients will be randomized to complete two visits
      with two single doses of treatment. Patients will be randomized in a cross-over manner.
      Treatment visits will be separated by a study medication wash-out period.Treatments will be
      administered in a blinded fashion.

      The patients will be male and female patients, ≥40 years of age, with a documented diagnosis
      of moderate or severe COPD according to Global Initiative for Chronic Obstructive Lung
      Disease (GOLD) criteria and >10-pack years history of smoking, FEV1 <80% and ≥30% of the
      predicted normal value.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Inspiratory Capacity (IC) Peak Value
time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
description: IC was measured with spirometry conducted according to internationally accepted standards. Peak IC was defined as the maximum IC of the mean at one of the post-dose measurements (30min, 60min, 120min, 180min and 240min).
measure: Forced Expiratory Volume in One Second (FEV1)
time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
description: FEV1 was measured with spirometry conducted according to internationally accepted standards. FEV1 was at 30, 60, 120, 180, and 240 minutes post-dose. Spirometry equipment and performance of spirometric testing had to be in accordance with standards as outlined in the American Thoracic Society for the Standardization of Spirometry recommendations. The spirometry equipment used during the study had to meet or exceed these minimal ATS recommendations
measure: Inspiratory Capacity (IC)
time frame: within 4h after dosing
description: During the 4 hours following inhalation of the study treatment, inspiratory capacity (IC) was measured with spirometry conducted according to internationally accepted standards. IC was measured at 30, 60, 120, 180, and 240 minutes post-dose
measure: Forced Volume Capacity (FVC)
time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
description: FVC was measured with spirometry conducted according to internationally accepted standards. Measurements were made 30, 60, 120, 180, and 240 minutes post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time
measure: Total Lung Capacity (TLC)
time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
description: TLC was measured with spirometry conducted according to internationally accepted standards. Peak TLC was calculated as the mean of the three Functional Residual Capacity peak measurements plus the mean of the three Inspiratory Capacity measurements which were measured each at 30, 60, 120, 180 and 240 minutes post dose
measure: Airway Resistance (Raw)
time frame: Day (0) 30minutes, 1, 2, 3, and 4 hours; Day (6) 30 minutes, 1, 2, 3, and 4 hours
description: Raw was measured with spirometry conducted according to internationally accepted standards. Raw was the mean of the measurements which were measured each at 30, 60, 120, 180 and 240 minutes
arm group label: Sequence A
arm group type: Placebo Comparator
description: Patients will inhale QAB149 (capsule form in blister packs) + Placebo via Novartis Concept 1 SDDPI
arm group label: Sequence B
arm group type: Active Comparator
description: Patients will inhale QAB149 plus NVA237 (capsule form in blister packs) via Novartis Concept 1 SDDPI
intervention type: Drug
intervention name: QAB149
description: Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
arm group label: Sequence A
arm group label: Sequence B
intervention type: Drug
intervention name: Placebo
description: Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
arm group label: Sequence A
intervention type: Drug
intervention name: NVA237
description: Capsule form in blister packs inhaled with the Novartis Concept 1 SDDPI
arm group label: Sequence B
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Corinne Wild, PhD
role: Study Director
affiliation: Novartis Pharmaceuticals
last name: Corinne Wild, PhD
role: Study Chair
affiliation: Novartis Pharmaceuticals
last name: Martin Brutsche, Prof. Dr. med.
role: Principal Investigator
affiliation: Kantonsspital St. Gallen, Switzerland
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Switzerland
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: 