<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/NCT02233543</url>
  </required_header>
  <id_info>
    <org_study_id>CQVA149ANO01</org_study_id>
    <nct_id>NCT02233543</nct_id>
  </id_info>
  <brief_title>A Multicenter, 4-week Crossover (Total Duration 12 Weeks) to Determine the Impact of QVA149 on Nocturnal Oxygen Levels in Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>A Multicenter, 4-week Crossover (Total Duration 12 Weeks), Placebo-controlled, Double-blind Study to Determine the Impact of QVA149 (Indacaterol/Glycopyrronium) 85/43 µg on Nocturnal Oxygen Levels in Chronic Obstructive Pulmonary Disease (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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study was to determine whether a fixed dose combination of indacaterol&#xD;
      and glycopyrronium (QVA149) has an impact on night-time blood oxygen levels in Chronic&#xD;
      Obstructive Pulmonary Disease.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 30, 2014</start_date>
  <completion_date type="Actual">June 26, 2016</completion_date>
  <primary_completion_date type="Actual">June 26, 2016</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Night-time Blood Oxygenation</measure>
    <time_frame>Post 4 weeks administration of QVA149, post 4 weeks administration of placebo</time_frame>
    <description>The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation</measure>
    <time_frame>Post 4 weeks administration of QVA149, post 4 weeks administration of placebo</time_frame>
    <description>The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>First QVA149 (indacaterol/glycopyrronium), then Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>First Placebo, then QVA149 (indacaterol/glycopyrronium)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QVA149</intervention_name>
    <description>Delivered once daily via single-dose dry powder inhaler</description>
    <arm_group_label>First Placebo, then QVA149 (indacaterol/glycopyrronium)</arm_group_label>
    <arm_group_label>First QVA149 (indacaterol/glycopyrronium), then Placebo</arm_group_label>
    <other_name>indacaterol/glycopyrronium,</other_name>
    <other_name>Ultibro Breezhaler</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QVA149 Placebo</intervention_name>
    <description>Placebo delivered once daily via single-dose dry powder inhaler</description>
    <arm_group_label>First Placebo, then QVA149 (indacaterol/glycopyrronium)</arm_group_label>
    <arm_group_label>First QVA149 (indacaterol/glycopyrronium), then Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of COPD (according to GOLD guidelines, updated 2014) with a&#xD;
             post-bronchodilator FEV1/FVC &lt;0.70&#xD;
&#xD;
          -  Patients with a post-bronchodilator FEV1 ≥30% and &lt;60% of the predicted normal value&#xD;
&#xD;
          -  Resting daytime oxygen saturation levels measured by pulse oximetry of ≤95% SpO2&#xD;
&#xD;
          -  Smoking history of at least 10 pack years (Ten pack-years are defined as 20 cigarettes&#xD;
             a day for 10 years, or 10 cigarettes a day for 20 years)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  An exacerbation of COPD (treatment with oral or parenteral antibiotics and/or&#xD;
             glucocorticosteroids and/or hospitalization related to COPD) within 4 weeks prior to&#xD;
             screening or during the run-in period&#xD;
&#xD;
          -  Diagnosed asthma&#xD;
&#xD;
          -  Patients receiving regular long term oxygen therapy (LTOT)&#xD;
&#xD;
          -  Ongoing / planned rehabilitation during the study period&#xD;
&#xD;
          -  Three or more awakenings during the night leading to toilet visit or other reasons for&#xD;
             exiting the bed during the last week prior to the screening visit due to non-COPD&#xD;
             reasons&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Aarhus</city>
        <zip>8000 C</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hvidovre</city>
        <zip>2650</zip>
        <country>Denmark</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bergen</city>
        <zip>-N5021</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Goteborg</city>
        <zip>413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Uppsala</city>
        <zip>SE-751 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Denmark</country>
    <country>Norway</country>
    <country>Sweden</country>
  </location_countries>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>August 19, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 8, 2014</study_first_posted>
  <results_first_submitted>June 20, 2017</results_first_submitted>
  <results_first_submitted_qc>November 10, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 6, 2018</results_first_posted>
  <last_update_submitted>November 10, 2017</last_update_submitted>
  <last_update_submitted_qc>November 10, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>QVA149</keyword>
  <keyword>nocturnal oxygen levels</keyword>
  <keyword>combination bronchodilator</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants were randomized in a 1:1 ratio.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>First QVA149 (Indacaterol/Glycopyrronium), Then Placebo</title>
          <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
        </group>
        <group group_id="P2">
          <title>First Placebo, Then QVA149 (Indacaterol/Glycopyrronium)</title>
          <description>Participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="13"/>
              </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>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participants required other treatment.</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </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="19"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="17">1 participant erroneously received QVA149 during both periods.</participants>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
              </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="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant required other treatment.</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>COPD exacerbation</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>
      <group_list>
        <group group_id="B1">
          <title>All Participants (QVA149/Placebo)</title>
          <description>Participants received 4 weeks of QVA149 and 4 weeks of placebo according to either of the following sequences: QVA149 first and then placebo, or placebo first and then QVA149.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="38"/>
          </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="68.4" spread="6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Night-time Blood Oxygenation</title>
        <description>The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
        <time_frame>Post 4 weeks administration of QVA149, post 4 weeks administration of placebo</time_frame>
        <population>Only randomized participants with data from both treatments were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 (Indacaterol/Glycopyrronium)</title>
            <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Night-time Blood Oxygenation</title>
          <description>The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
          <population>Only randomized participants with data from both treatments were analyzed.</population>
          <units>Percent Oxygenation</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="89.59" spread="0.30"/>
                    <measurement group_id="O2" value="90.04" spread="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2419</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.21</ci_lower_limit>
            <ci_upper_limit>0.32</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation</title>
        <description>The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
        <time_frame>Post 4 weeks administration of QVA149, post 4 weeks administration of placebo</time_frame>
        <population>Only randomized participants with data from both treatments were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 (Indacaterol/Glycopyrronium)</title>
            <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation</title>
          <description>The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.</description>
          <population>Only randomized participants with data from both treatments were analyzed.</population>
          <units>Percent</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
                <count group_id="O2" value="34"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.37" spread="5.09"/>
                    <measurement group_id="O2" value="36.58" spread="4.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.2016</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>7.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.51</ci_lower_limit>
            <ci_upper_limit>20.08</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>QVA149 (Indacaterol/Glycopyrronium)</title>
          <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</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="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA (17.0)</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="14" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blindness transient</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthritis reactive</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </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="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Laryngospasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="34"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="34"/>
              </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/NCT02233543
org study id: CQVA149ANO01
nct id: NCT02233543
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study was to determine whether a fixed dose combination of indacaterol
      and glycopyrronium (QVA149) has an impact on night-time blood oxygen levels in Chronic
      Obstructive Pulmonary Disease.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Mean Night-time Blood Oxygenation
time frame: Post 4 weeks administration of QVA149, post 4 weeks administration of placebo
description: The mean night-time blood oxygenation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.
measure: Percent of Time Spent During the Night Below 90 % in Blood Oxygen Saturation
time frame: Post 4 weeks administration of QVA149, post 4 weeks administration of placebo
description: The time during the night spent below 90 % in blood oxygen saturation following 4 weeks administration of QVA149 compared to placebo was assessed. Night time oxygenation (SpO2) was measured using polygraphy.
arm group label: First QVA149 (indacaterol/glycopyrronium), then Placebo
arm group type: Experimental
description: Participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.
arm group label: First Placebo, then QVA149 (indacaterol/glycopyrronium)
arm group type: Experimental
description: Participants received 4 weeks of placebo once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day followed by 2 weeks washout. Then participants received 4 weeks of QVA149 85/43 μg delivered dose once daily in the morning between 08:00 and 11:00 AM at approximately the same time every day.
intervention type: Drug
intervention name: QVA149
description: Delivered once daily via single-dose dry powder inhaler
arm group label: First Placebo, then QVA149 (indacaterol/glycopyrronium)
arm group label: First QVA149 (indacaterol/glycopyrronium), then Placebo
other name: indacaterol/glycopyrronium,
other name: Ultibro Breezhaler
intervention type: Drug
intervention name: QVA149 Placebo
description: Placebo delivered once daily via single-dose dry powder inhaler
arm group label: First Placebo, then QVA149 (indacaterol/glycopyrronium)
arm group label: First QVA149 (indacaterol/glycopyrronium), then Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: Denmark
country: Norway
country: Sweden
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
sharing ipd: Undecided
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 