<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/NCT02202616</url>
  </required_header>
  <id_info>
    <org_study_id>CQVA149ACA01</org_study_id>
    <nct_id>NCT02202616</nct_id>
  </id_info>
  <brief_title>Prospective Cohort Study for the Real - Life Effectiveness Evaluation of GlycOpyrronium With IndacatERol Combination in the Management of COPD in Canada (POWER Study)</brief_title>
  <acronym>POWER</acronym>
  <official_title>Prospective Cohort Study for the Real - Life Effectiveness Evaluation of GlycOpyrronium With IndacatERol Combination in the Management of COPD in Canada (POWER Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</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>
      This is a single cohort, prospective post approval study conducted on patients with COPD in&#xD;
      Canada. The study will enroll patients that have not responded to their current treatment of&#xD;
      tiotropium alone, or who are on the fixed dose combinations fluticasone&#xD;
      propionate/salmeterol. Only patients for whom the physician has decided to change treatment&#xD;
      due to lack of efficacy will be eligible to be enrolled in the study.&#xD;
&#xD;
      Also will evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium&#xD;
      50 mcg) in the management of patients.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 27, 2014</start_date>
  <completion_date type="Actual">April 5, 2017</completion_date>
  <primary_completion_date type="Actual">April 5, 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)</measure>
    <time_frame>16 weeks study</time_frame>
    <description>Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4</measure>
    <time_frame>Baseline, week 4</time_frame>
    <description>Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)</measure>
    <time_frame>Baseline, Week 4, week 16</time_frame>
    <description>A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)</measure>
    <time_frame>Baseline, week 4, week 16</time_frame>
    <description>The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">401</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>ULTIBRO BREEZHALER</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrronium /Indacaterol maleate</intervention_name>
    <description>Glycopyrronium 50mcg/Indacaterol maleate 110mcg once daily by a breezhaler device</description>
    <arm_group_label>ULTIBRO BREEZHALER</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient diagnosed and treated for moderate to severe COPD according to the Global&#xD;
             Initiative for Chronic Obstructive Lung Disease according to physician's assessment&#xD;
&#xD;
          -  Smoking history of &gt; 10 pack - years.&#xD;
&#xD;
          -  On-going treatment with tiotropium or fixed dose combination of LABA/ICS, specifically&#xD;
             combinations fluticasone propionate/salmeterol for a minimum of three months but&#xD;
             demonstrating persistence of symptoms indicating change of treatment to combination&#xD;
             therapy **using a CAT score &gt; 10.&#xD;
&#xD;
          -  Treatment with QVA149 is indicated as per the product monograph and appropriate for&#xD;
             the patient as per the judgment of the treating physician.&#xD;
&#xD;
          -  Patient has signed informed consent agreeing to participate in the study and undergo&#xD;
             the study treatments and allowing the use of their data for the purposes of the study.&#xD;
&#xD;
          -  Patient is expected to be available for 16 weeks after study enrolment&#xD;
&#xD;
               -  Assessed as per routine care or as documented in the patient's chart. ** As&#xD;
                  determined and decided by the treating physician prior to enrolment of the&#xD;
                  patient in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Patients fulfilling any of the following criteria are not eligible for inclusion in this&#xD;
        study. No additional exclusions may be applied by the investigator, in order to ensure that&#xD;
        the study population will be representative of all eligible patients.&#xD;
&#xD;
          -  Patients not willing to sign an informed consent.&#xD;
&#xD;
          -  Patient on maintenance treatment including triple therapy (LABA +LAMA+ICS) for COPD&#xD;
&#xD;
          -  Patients with a diagnosis of asthma or history of asthma.&#xD;
&#xD;
          -  Patients who have had two or more moderate to severe exacerbations during the last 12&#xD;
             months prior to study enrolment. A moderate COPD exacerbation is defined by&#xD;
             requirement for treatment with systemic corticosteroids or antibiotics or both. A&#xD;
             severe COPD exacerbation is defined by hospitalization, including an emergency room&#xD;
             visit of longer than 24 h.&#xD;
&#xD;
          -  Patients who had an exacerbation within the previous 6 weeks to enrolment.&#xD;
&#xD;
          -  Patients who as per physician clinical judgment will require ICS treatment&#xD;
             co-administered with QVA149 during the study period.&#xD;
&#xD;
          -  Patients with other chronic respiratory conditions that may affect the outcome of&#xD;
             treatment including but not limited to lung cancer.&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St-Charles-Borromée</city>
        <state>Quebec</state>
        <zip>J6E 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>June 26, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 29, 2014</study_first_posted>
  <results_first_submitted>March 20, 2018</results_first_submitted>
  <results_first_submitted_qc>March 28, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 24, 2019</results_first_posted>
  <last_update_submitted>June 25, 2019</last_update_submitted>
  <last_update_submitted_qc>June 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD,</keyword>
  <keyword>QVA149,</keyword>
  <keyword>Tiotropium,</keyword>
  <keyword>FDC,</keyword>
  <keyword>GlycOpyrronium With IndacatERol,</keyword>
  <keyword>POWER</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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 3, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT02202616/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 14, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/16/NCT02202616/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>QVA149 110/50</title>
          <description>QVA149 110/50- Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="401"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Intent to Treat Set (ITT)</title>
              <participants_list>
                <participants group_id="P1" count="338"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="301"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="100"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screen failed</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Administrative problems</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Abnormal test procedure result</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Unsatisfactory therapeutic effect</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The ITT included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
      <group_list>
        <group group_id="B1">
          <title>ULTIBRO BREEZHALER</title>
          <description>Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="338"/>
          </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="66.1" spread="9.46"/>
                  </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="149"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="189"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="330"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)</title>
        <description>Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks.</description>
        <time_frame>16 weeks study</time_frame>
        <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 110/50 After Flu/Sal</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol</description>
          </group>
          <group group_id="O2">
            <title>QVA149 110/50 After Tio</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)</title>
          <description>Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score &gt;10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks.</description>
          <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
          <units>Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="83"/>
                <count group_id="O2" value="235"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.17" spread="0.397"/>
                    <measurement group_id="O2" value="0.18" spread="0.321"/>
                  </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>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.17</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.340</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.14</ci_lower_limit>
            <ci_upper_limit>0.21</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4</title>
        <description>Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial</description>
        <time_frame>Baseline, week 4</time_frame>
        <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 110/50 After Flu/Sal</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol</description>
          </group>
          <group group_id="O2">
            <title>QVA149 110/50 After Tio</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4</title>
          <description>Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial</description>
          <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
          <units>Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="79"/>
                <count group_id="O2" value="224"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" spread="0.308"/>
                    <measurement group_id="O2" value="0.14" spread="0.267"/>
                  </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>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.14</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>0.278</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.11</ci_lower_limit>
            <ci_upper_limit>0.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)</title>
        <description>A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16.</description>
        <time_frame>Baseline, Week 4, week 16</time_frame>
        <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 110/50 After Flu/Sal</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol</description>
          </group>
          <group group_id="O2">
            <title>QVA149 110/50 After Tio</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium</description>
          </group>
        </group_list>
        <measure>
          <title>Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)</title>
          <description>A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16.</description>
          <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
          <units>Score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="87"/>
                <count group_id="O2" value="248"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>BDI week 0</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="86"/>
                    <count group_id="O2" value="245"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.5" spread="2.07"/>
                    <measurement group_id="O2" value="6.8" spread="2.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TDI week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="79"/>
                    <count group_id="O2" value="226"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.2" spread="2.72"/>
                    <measurement group_id="O2" value="2.0" spread="2.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TDI week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="84"/>
                    <count group_id="O2" value="237"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9" spread="3.28"/>
                    <measurement group_id="O2" value="2.4" spread="2.78"/>
                  </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>
            <groups_desc>Week 4</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.0</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2.47</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.74</ci_lower_limit>
            <ci_upper_limit>2.30</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 16</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>2.5</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>2.92</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.21</ci_lower_limit>
            <ci_upper_limit>2.85</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)</title>
        <description>The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.</description>
        <time_frame>Baseline, week 4, week 16</time_frame>
        <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 110/50 After Flu/Sal</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with FDC of fluticasone propionate and salmeterol</description>
          </group>
          <group group_id="O2">
            <title>QVA149 110/50 After Tio</title>
            <description>QVA149 110/50 combination of (indacaterol maleate 110 µg and glycopyrronium bromide 50 µg) after patients treated with tiotropium</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)</title>
          <description>The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.</description>
          <population>Intent to treat set (ITT)- included all patients who received the study treatment and returned for ≥ 1 post baseline visit</population>
          <units>Score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="83"/>
                <count group_id="O2" value="234"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.9" spread="7.55"/>
                    <measurement group_id="O2" value="-4.7" spread="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.2" spread="8.34"/>
                    <measurement group_id="O2" value="-5.9" spread="6.44"/>
                  </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>
            <groups_desc>Week 4</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-5.0</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>6.25</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.7</ci_lower_limit>
            <ci_upper_limit>-4.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 16</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-6.5</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>7.03</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.3</ci_lower_limit>
            <ci_upper_limit>-5.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From week 0 to week 16</time_frame>
      <group_list>
        <group group_id="E1">
          <title>QVA149 110/50</title>
          <description>QVA149 110/50-Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (19.1)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Lymphadenopathy mediastinal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intestinal ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Wound</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Hepatic cancer metastatic</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </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="373"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Pulmonary mass</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <default_vocab>MedDRA (19.1)</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="56" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="373"/>
              </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="13" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="373"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="373"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="373"/>
              </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>
      <email>Novartis.email@novartis.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02202616
org study id: CQVA149ACA01
nct id: NCT02202616
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single cohort, prospective post approval study conducted on patients with COPD in
      Canada. The study will enroll patients that have not responded to their current treatment of
      tiotropium alone, or who are on the fixed dose combinations fluticasone
      propionate/salmeterol. Only patients for whom the physician has decided to change treatment
      due to lack of efficacy will be eligible to be enrolled in the study.

      Also will evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium
      50 mcg) in the management of patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Trough (Forced Expiratory Volume (FEV1) (Pre-dose FEV1)
time frame: 16 weeks study
description: Primary end points: To evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score >10 with tiotropium monotherapy; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks. and to evaluate the real-life effectiveness of QVA149 (indacaterol 110 mcg/glycopyrronium 50 mcg) in the management of patients with COPD who have symptoms defined as CAT score >10 while on treatment with FDC of fluticasone propionate/salmeterol; effectiveness will be assessed as the mean change in trough FEV1 from baseline to 16 weeks.
measure: Change From Baseline in Trough FEV1 (Forced Expiratory Volume) to Week 4
time frame: Baseline, week 4
description: Portable spirometers will be provided to investigators and they will use this device for all of their patient measurements of FEV1 during the trial
measure: Single Point and Change in Baseline Dyspnea Index and Transitional Dyspnea Index (BDI/TDI)
time frame: Baseline, Week 4, week 16
description: A trained assessor interviewed the patient and graded the degree of impairment due to dyspnea (difficulty breathing). BDI/TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort and captures changes from baseline. BDI was measured at day 1 prior to the first dose with domain scores ranging from 0=very severe to 4=no impairment and a total score ranging from 0 to 12(best). TDI captures changes from baseline. Each domain is scored from -3=major deterioration to 3=major improvement to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score. The BDI was assessed at Baseline, whereas the TDI was assessed at Week 4 and Week 16.
measure: Change From Baseline in Chronic Obstructive Pulmonary Disease (COPD) Assessment Questionnaire (CAT)
time frame: Baseline, week 4, week 16
description: The CAT is an 8 item questionnaire that assesses the impact of COPD on the patient's functional status. Scores for each of the 8 items are summed to give an overall score (out of 40). The score ranges from 0-40 where higher scores represent worse health status. CAT scores ≥ 10 are associated with significantly impaired health status.
arm group label: ULTIBRO BREEZHALER
arm group type: Other
description: Patients diagnosed with chronic obstructive pulmonary disorder (COPD) who are symptomatic (CAT score over 10) and who are treated with Tiotropium (SPIRIVA HANDALER) or Fluticasone propionate/Salmeterol- ADVAIR DISKUS (FDC).
intervention type: Drug
intervention name: Glycopyrronium /Indacaterol maleate
description: Glycopyrronium 50mcg/Indacaterol maleate 110mcg once daily by a breezhaler device
arm group label: ULTIBRO BREEZHALER
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 