<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/NCT01709903</url>
  </required_header>
  <id_info>
    <org_study_id>CQVA149A2331</org_study_id>
    <nct_id>NCT01709903</nct_id>
  </id_info>
  <brief_title>A 26-week Treatment Randomized, Double-blind, Double Dummy Study to Assess the Efficacy and Safety of QVA149</brief_title>
  <official_title>A 26-week Treatment Randomized, Double-blind, Double Dummy, Parallel-group Study to Assess the Efficacy and Safety of QVA149 (Indacaterol / Glycopyrronium Bromide) Compared to Fluticasone/Salmeterol in Patients With Moderate to 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>
      To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50&#xD;
      µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours&#xD;
      15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with&#xD;
      moderate to severe COPD&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50&#xD;
      µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours&#xD;
      15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with&#xD;
      moderate to severe COPD.&#xD;
&#xD;
      The study population will consist of approximate 736 male and female adults (age 40 years and&#xD;
      greater) with a clinical diagnosis of stable COPD [GOLD (2010)] and a smoking history of at&#xD;
      least 10 pack years. It is anticipated that approximately 981 patients will need to be&#xD;
      screened in order to randomize 736 patients into 2 treatment arms of the study with an equal&#xD;
      randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients).&#xD;
      Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It&#xD;
      is intended that 552 patients will complete the study at Week 26 without major protocol&#xD;
      deviations. Dropouts will not be replaced.&#xD;
&#xD;
      This will be a multi-national study, including China, and at least two other countries.&#xD;
&#xD;
      Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50&#xD;
      patients per treatment arm) in pre-selected centers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">February 2014</completion_date>
  <primary_completion_date type="Actual">February 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</measure>
    <time_frame>26 weeks</time_frame>
    <description>Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</measure>
    <time_frame>26 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours</measure>
    <time_frame>Day 1, 12 and 26 weeks</time_frame>
    <description>Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period</measure>
    <time_frame>6,12,18 and 26 weeks</time_frame>
    <description>Average of Trough Forced Expiratory Volume in one second (FEV1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of Trough FVC (L) Over the Whole Treatment Period</measure>
    <time_frame>12 and 26 weeks</time_frame>
    <description>Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment</measure>
    <time_frame>26 weeks</time_frame>
    <description>A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Analysis of the TDI Focal Score Over the Whole Treatment Period</measure>
    <time_frame>12 and 26 weeks</time_frame>
    <description>The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. .&quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals</measure>
    <time_frame>12 and 26 weeks</time_frame>
    <description>The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. &quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment</measure>
    <time_frame>26 weeks</time_frame>
    <description>Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">744</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>QVA149</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>fluticasone/salmeterol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QVA149</intervention_name>
    <description>QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).</description>
    <arm_group_label>QVA149</arm_group_label>
    <other_name>Experimental: QVA149</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone/salmeterol</intervention_name>
    <description>Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.</description>
    <arm_group_label>fluticasone/salmeterol</arm_group_label>
    <other_name>Comparator: Fluticasone/salmeterol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to QVA149</intervention_name>
    <description>Placebo to QVA149 with SDDPI</description>
    <arm_group_label>fluticasone/salmeterol</arm_group_label>
    <other_name>Experimental: QVA149</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo to fluticasone/salmeterol</intervention_name>
    <description>Placebo to fluticasone/salmeterol with Accuhaler</description>
    <arm_group_label>QVA149</arm_group_label>
    <other_name>Comparator: fluticasone/salmeterol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with moderate to severe stable COPD (Stage II or Stage III) according to&#xD;
             Global Initiative for Chronic Obstructive Lung Disease (GOLD) Guideline.&#xD;
&#xD;
        Current or ex-smokers who have a smoking history of at least 10 pack years. Patients with a&#xD;
        post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥ 30% and &lt; 80% of the&#xD;
        predicted normal, and post-bronchodilator FEV1/FVC &lt; 0.7.&#xD;
&#xD;
        Modified Medical Research Council (mMRC) grade of at least 2 at Visit 2.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a&#xD;
             female after conception and until the termination of gestation, confirmed by a&#xD;
             positive Human Chorionic Gonadotropin (hCG) laboratory test.&#xD;
&#xD;
        Patents with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia (BPH),&#xD;
        bladder-neck obstruction, moderate to severe renal impairment or urinary retention. BPH&#xD;
        patients who are stable on treatment can be considered.&#xD;
&#xD;
        Patients with a history of long QT syndrome or whose QTc measured at run-in (Visit 2)&#xD;
        (Fridericia method) is prolonged (&gt;450 ms for males and females) as confirmed by the&#xD;
        central Electrocardiogram (ECG) assessor.&#xD;
&#xD;
        Patients with Type I or uncontrolled Type II diabetes. Patients who have not achieved&#xD;
        spirometry result at Visit 2 in accordance with American Thoracic Society/European&#xD;
        Respiratory Society (ATS/ERS) criteria for acceptability and repeatability.&#xD;
&#xD;
        Patients with, a) any history of asthma or, b) onset of respiratory symptoms prior to age&#xD;
        40 years.&#xD;
&#xD;
        Patients with concomitant pulmonary disease (e.g. lung fibrosis, primary bronchiectasis,&#xD;
        sarcoidosis, interstitial lung disorder, pulmonary hypertension).&#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>
  <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>Caba</city>
        <state>Buenos Aires</state>
        <zip>1122</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>B8000XAV</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1056ABJ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1280AEB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1424BSF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Caba</city>
        <state>Buenos Aires</state>
        <zip>C1425BEN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <zip>1900</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>7600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rojas</city>
        <state>Buenos Aires</state>
        <zip>B2705XAE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Miguel de Tucuman</city>
        <state>Tucuman</state>
        <zip>T4000IFL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1125ABE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cordoba</city>
        <zip>X5016KEH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Santiago</city>
        <state>Region Metropolitana</state>
        <zip>8431633</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Santiago</city>
        <state>Region Metropolitana</state>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Viña del Mar</city>
        <state>Vina del Mar</state>
        <zip>2520024</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Santiago</city>
        <zip>Piso 1</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Santiago</city>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100023</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nanning</city>
        <state>Guangxi</state>
        <zip>530021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shijiazhuang</city>
        <state>Hebei</state>
        <zip>050000</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <zip>430022</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Changsha City</city>
        <state>Hunan</state>
        <zip>410011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Changsha</city>
        <state>Hunan</state>
        <zip>410003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <zip>210029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <zip>215004</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nanchang</city>
        <state>Jiangxi</state>
        <zip>330006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shengyang</city>
        <state>Liaoning</state>
        <zip>110016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shenyang</city>
        <state>Liaoning</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Qingdao</city>
        <state>Shandong</state>
        <zip>266011</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Xi'an</city>
        <state>Shanxi</state>
        <zip>710032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Xi'an</city>
        <state>Shanxi</state>
        <zip>710061</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chengdu</city>
        <state>Sichuan</state>
        <zip>610041</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310006</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310016</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100020</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100029</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100034</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <zip>100050</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400037</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400038</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chongqing</city>
        <zip>400042</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jiangyin</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nanjing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200080</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shanghai</city>
        <zip>200433</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei</city>
        <state>Taiwan, ROC</state>
        <zip>112</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kaohsiung</city>
        <zip>81346</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lin-Ko</city>
        <zip>33305</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Niaosong Township</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taichung</city>
        <zip>40705</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Taipei County</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>China</country>
    <country>Taiwan</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
  </removed_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>February 27, 2015</results_first_submitted>
  <results_first_submitted_qc>March 13, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 17, 2015</results_first_posted>
  <last_update_submitted>March 13, 2015</last_update_submitted>
  <last_update_submitted_qc>March 13, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 17, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic obstructive pulmonary disease</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>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Glycopyrrolate</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Fluticasone-Salmeterol Drug Combination</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were randomized into 2 treatment arms of the study with an equal 1:1 randomization ratio: QVA149 and Flut/Salm</recruitment_details>
      <pre_assignment_details>A total of 1189 patients were screened; 744 (62.6%) completed the screening phase while 445 (37.4%) patients discontinued prior to completion of the screening phase</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>QVA149</title>
          <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
        </group>
        <group group_id="P2">
          <title>Fluticasone/Salmeterol</title>
          <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="372">Randomized set</participants>
                <participants group_id="P2" count="372">Randomized set</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="343"/>
                <participants group_id="P2" count="333"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>administrative problems</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Abnormal test procedure results</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>In ability to use device</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>no longer needed study drug</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Three patients in the Flut/Salm treatment arm: were excluded from the FAS, safety set and PPS as they were randomized in error and did not receive the study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>QVA149</title>
          <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
        </group>
        <group group_id="B2">
          <title>Fluticasone/Salmeterol</title>
          <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</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="372"/>
            <count group_id="B2" value="369"/>
            <count group_id="B3" value="741"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Safety Set</description>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.8" spread="7.82"/>
                    <measurement group_id="B2" value="65.3" spread="7.91"/>
                    <measurement group_id="B3" value="65.0" spread="7.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Safety Set</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="31"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="341"/>
                    <measurement group_id="B2" value="331"/>
                    <measurement group_id="B3" value="672"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Safety Set</description>
          <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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="314"/>
                    <measurement group_id="B2" value="309"/>
                    <measurement group_id="B3" value="623"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="58"/>
                    <measurement group_id="B3" value="113"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</title>
        <description>Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.</description>
        <time_frame>26 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</title>
          <description>Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.</description>
          <population>FAS</population>
          <units>liters</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.248" spread="0.0173"/>
                    <measurement group_id="O2" value="1.176" spread="0.0172"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</title>
        <time_frame>26 weeks</time_frame>
        <population>FAS</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d</title>
          <population>FAS</population>
          <units>liters</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.259" spread=".0170"/>
                    <measurement group_id="O2" value="1.183" spread="0.0168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours</title>
        <description>Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.</description>
        <time_frame>Day 1, 12 and 26 weeks</time_frame>
        <population>Full Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours</title>
          <description>Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.</description>
          <population>Full Analysis set</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (n=369,364)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.317" spread="0.0096"/>
                    <measurement group_id="O2" value="1.252" spread="0.0094"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks (n=350,338)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.388" spread="0.0163"/>
                    <measurement group_id="O2" value="1.262" spread="0.0161"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>26 weeks (n=339,323)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.351" spread="0.0167"/>
                    <measurement group_id="O2" value="1.229" spread="0.0167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period</title>
        <description>Average of Trough Forced Expiratory Volume in one second (FEV1)</description>
        <time_frame>6,12,18 and 26 weeks</time_frame>
        <population>Full analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period</title>
          <description>Average of Trough Forced Expiratory Volume in one second (FEV1)</description>
          <population>Full analysis set</population>
          <units>liter</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 6 (n=356,341)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.256" spread="0.0151"/>
                    <measurement group_id="O2" value="1.184" spread="0.0149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 12 (n=346,333)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.265" spread="0.0158"/>
                    <measurement group_id="O2" value="1.191" spread="0.0156"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 18 (n=339,332)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.252" spread="0.0166"/>
                    <measurement group_id="O2" value="1.174" spread="0.0164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 26 (n=338,324)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.226" spread="0.0171"/>
                    <measurement group_id="O2" value="1.142" spread="0.0171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Analysis of Trough FVC (L) Over the Whole Treatment Period</title>
        <description>Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose</description>
        <time_frame>12 and 26 weeks</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Analysis of Trough FVC (L) Over the Whole Treatment Period</title>
          <description>Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose</description>
          <population>Full Analysis Set</population>
          <units>liter</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (n=350,351)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.040" spread="0.0288"/>
                    <measurement group_id="O2" value="2.957" spread="0.0280"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 (n=342,332)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.036" spread="0.0304"/>
                    <measurement group_id="O2" value="2.835" spread="0.0302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 26 (n= 333,323)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.966" spread="0.0334"/>
                    <measurement group_id="O2" value="2.793" spread="0.0333"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment</title>
        <description>A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.</description>
        <time_frame>26 weeks</time_frame>
        <population>Full Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment</title>
          <description>A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.</description>
          <population>Full Analysis set</population>
          <units>numbers on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 26 (n= 340,329)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.20" spread="1.118"/>
                    <measurement group_id="O2" value="32.00" spread="1.118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 26 LOCF(n=354,342)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31.74" spread="1.136"/>
                    <measurement group_id="O2" value="32.43" spread="1.130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Analysis of the TDI Focal Score Over the Whole Treatment Period</title>
        <description>The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. .&quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point.</description>
        <time_frame>12 and 26 weeks</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Analysis of the TDI Focal Score Over the Whole Treatment Period</title>
          <description>The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. .&quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point.</description>
          <population>Full Analysis Set</population>
          <units>Numbers on a scale</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline 12 weeks (n=348,337)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.36" spread="0.096"/>
                    <measurement group_id="O2" value="6.36" spread="0.104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 weeks (n=348,337)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.62" spread="0.240"/>
                    <measurement group_id="O2" value="2.40" spread="0.238"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline 26 weeks (n=335,326)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.38" spread="0.097"/>
                    <measurement group_id="O2" value="6.40" spread="0.105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>26 weeks (n=335,326)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.02" spread="0.266"/>
                    <measurement group_id="O2" value="2.86" spread="0.266"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals</title>
        <description>The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. &quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.</description>
        <time_frame>12 and 26 weeks</time_frame>
        <population>Full Analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals</title>
          <description>The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. &quot;Baseline 12 weeks&quot; and &quot;Baseline 26 weeks&quot;, were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.</description>
          <population>Full Analysis set</population>
          <units># of puffs</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Daytime 12-16 weeks (n=329,318)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.57" spread="1.934"/>
                    <measurement group_id="O2" value="1.69" spread="2.130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daytime 12-16 weeks (n=329,318)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.66" spread="1.185"/>
                    <measurement group_id="O2" value="0.61" spread="1.117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Nighttime 12-16 weeks (n=322,307)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.25" spread="1.5954"/>
                    <measurement group_id="O2" value="1.24" spread="1.707"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nighttime 12-16 weeks (n=322,307)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52" spread="1.007"/>
                    <measurement group_id="O2" value="0.49" spread="0.960"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Daytime 24-26 weeks (n=326,315)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.54" spread="1.885"/>
                    <measurement group_id="O2" value="1.70" spread="2.160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daytime 24-26 weeks (n=326,315)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.63" spread="1.226"/>
                    <measurement group_id="O2" value="0.62" spread="1.135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Night time 24-26 weeks (n=320,304)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.23" spread="1.588"/>
                    <measurement group_id="O2" value="1.21" spread="1.702"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Night time 24-26 weeks (n=320,304)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52" spread="1.087"/>
                    <measurement group_id="O2" value="0.48" spread="0.923"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment</title>
        <description>Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)</description>
        <time_frame>26 weeks</time_frame>
        <population>Full Analysis Set</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149</title>
            <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone/Salmeterol</title>
            <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
          </group>
        </group_list>
        <measure>
          <title>Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment</title>
          <description>Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)</description>
          <population>Full Analysis Set</population>
          <units>% days in study</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="372"/>
                <count group_id="O2" value="369"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>% nights 'no nighttime awakenings' (n=336,322)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.57" spread="2.138"/>
                    <measurement group_id="O2" value="67.86" spread="2.101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% days with 'no daytime symptoms' (n=341,334)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.31" spread="1.466"/>
                    <measurement group_id="O2" value="10.22" spread="1.425"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% days able perform daily activities (n=341,334)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.02" spread="2.200"/>
                    <measurement group_id="O2" value="42.16" spread="2.140"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>QVA149 110mcg/50mcg</title>
          <description>QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg</description>
        </group>
        <group group_id="E2">
          <title>Salmeterol/Fluticasone 50mcg/500mcg</title>
          <description>Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Arteriosclerosis coronary artery</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cor pulmonale</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cor pulmonale chronic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Right ventricular dysfunction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Conjunctivitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Pterygium</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Inguinal hernia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperplasia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Sudden cardiac death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Hepatic failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Hepatic function abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </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="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Type 2 diabetes mellitus</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Rectal cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebral infarction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </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="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Lung cyst</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Pneumothorax spontaneous</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</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="107" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="135" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="30" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="45" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection bacterial</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="369"/>
              </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="69" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="83" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="369"/>
              </event>
              <event>
                <sub_title>Oropharyngeal pain</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="369"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="372"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="369"/>
              </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 (ie, data from all sites) in the clinical trial</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/NCT01709903
org study id: CQVA149A2331
nct id: NCT01709903
lead sponsor: 
has dmc: No
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50
      µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours
      15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with
      moderate to severe COPD
To demonstrate the non-inferiority of QVA149 110/50 µg o.d. to fluticasone/salmeterol 500/50
      µg b.i.d. in terms of trough Forced Expiratory Volume in one second (FEV1) (mean of 23 hours
      15 min and 23 hours 45 min post QVA149 dose) following 26 weeks of treatment in patients with
      moderate to severe COPD.

      The study population will consist of approximate 736 male and female adults (age 40 years and
      greater) with a clinical diagnosis of stable COPD [GOLD (2010)] and a smoking history of at
      least 10 pack years. It is anticipated that approximately 981 patients will need to be
      screened in order to randomize 736 patients into 2 treatment arms of the study with an equal
      randomization ratio, meaning QVA149 (368 patients), fluticasone/salmeterol (368 patients).
      Treatment randomization will be stratified by current/ex-smoker status and prior ICS use. It
      is intended that 552 patients will complete the study at Week 26 without major protocol
      deviations. Dropouts will not be replaced.

      This will be a multi-national study, including China, and at least two other countries.

      Standardization FEV1 AUC0-12h will be performed in a subgroup of around 100 patients (50
      patients per treatment arm) in pre-selected centers.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Non-inferiority of QVA149 110/50 μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
time frame: 26 weeks
description: Measurement of QVA149 110/50 μg o.d. to fluticasone/salmeterol 500/50 μg b.i.d. in terms of trough FEV1 (mean of 23 h 15 min and 23 h 45 min post QVA149 dose) following 26 weeks of treatment in patients with moderate to severe COPD.
measure: Trough Forced Expiratory Volume in One Second (FEV1) Following 26 Weeks of Treatment to Demonstrate the Superiority of QVA 110/50μg o.d. to Fluticasone/Salmeterol 500/50 μg b.i.d
time frame: 26 weeks
measure: Standardized Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) 0-4 Hours
time frame: Day 1, 12 and 26 weeks
description: Forced Expiratory Volume in 1 Second (FEV1) Area Under the Curve (AUC) 0-4h at Day 1 was measured via spirometry conducted according to internationally accepted standards. Measurements were made at 0, 5, 15, and 30 minutes; and 1, 2, 3 and 4 hours post-dose. The standardized AUC FEV1 was calculated as the sum of trapezoids divided by the length of time. Mixed model used: AUC FEV1 = treatment + baseline FEV1 + FEV1 reversibility components + baseline smoking status + baseline ICS use + country + center (country) + error. Center was included as a random effect nested within country.
measure: Analysis of FEV1 (L) Trough Response (Pre-dose) Over the Whole Treatment Period
time frame: 6,12,18 and 26 weeks
description: Average of Trough Forced Expiratory Volume in one second (FEV1)
measure: Analysis of Trough FVC (L) Over the Whole Treatment Period
time frame: 12 and 26 weeks
description: Average of Trough Forced Vital Capacity (FVC) at 23 hours 15 min and the 23 hours 45 min post dose
measure: Health Related Quality of Life Analysis of SGRQ Total Score After 26 Weeks of Treatment
time frame: 26 weeks
description: A Total and three component scores are calculated: Symptoms; Activity; Impacts. Each component of the questionnaire is scored separately:The score for each component is calculated separately by dividing the summed weights by the maximum possible weight for that component and expressing the result as a percentage: Score = 100 x Summed weights from all positive items in that component divided by Sum of weights for all items in that component The Total score is calculated in similar way: Score = 100 x Summed weights from all positive items in the questionnaire divided by Sum of weights for all items in the questionnaire Sum of maximum possible weights for each component and Total: Symptoms 566.2 Activity 982.9 Impacts 1652.8 Total (sum of maximum for all three components) 3201.9 The proportion of patients who achieve a clinically important improvement of at least 4 units in the total SGRQ will be analyzed. The higher the score the more symptoms of disease are present.
measure: Analysis of the TDI Focal Score Over the Whole Treatment Period
time frame: 12 and 26 weeks
description: The Transition Dyspnea Index (TDI) total score after 12 and 26 weeks of treatment will be analyzed using the same mixed model as specified for the primary analysis with the Baseline Dyspnea Index (BDI) total score as the baseline.Total score ranging - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea. One additional option in each category, which does not contribute to the score, allows for circumstances in which impairment is due to reasons other than dyspnea. ."Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point.
measure: Rescue Medication Use: Summary of the Mean Daily, Daytime and Nighttime Number of Puffs of Rescue Medication, by 4 Weekly Intervals
time frame: 12 and 26 weeks
description: The number of puffs of rescue medication taken in the previous 12 hours will be recorded in the Patient Diary in the morning and evening. "Baseline 12 weeks" and "Baseline 26 weeks", were the baseline scores for available participants analyzed for each time point. Less puffs taken is better.
measure: Symptoms Reported Using E-diary Over 12 and 26 Weeks of Treatment
time frame: 26 weeks
description: Percentage of nights with 'no nighttime awakenings', percentage of days with 'no daytime symptoms', and percentage of 'days able to perform usual daily activities' over 26 weeks (FAS)
arm group label: QVA149
arm group type: Experimental
description: QVA149 110/50 µg o.d., delivered via a single-dose dry powder inhaler (SDDPI), consisting of a fixed dose combination of indacaterol 110µg and NVA237 50µg
arm group label: fluticasone/salmeterol
arm group type: Active Comparator
description: Fluticasone/salmeterol 500/50 µg b.i.d., delivered via a dry powder inhaler Accuhaler® device
intervention type: Drug
intervention name: QVA149
description: QVA149 110/50 µg capsules q.d. for inhalation, delivered via Novartis single dose dry powder inhaler (SDDPI).
arm group label: QVA149
other name: Experimental: QVA149
intervention type: Drug
intervention name: Fluticasone/salmeterol
description: Active fluticasone/salmeterol (500/50µg) b.i.d via a dry power inhaler Accuhaler® device.
arm group label: fluticasone/salmeterol
other name: Comparator: Fluticasone/salmeterol
intervention type: Drug
intervention name: Placebo to QVA149
description: Placebo to QVA149 with SDDPI
arm group label: fluticasone/salmeterol
other name: Experimental: QVA149
intervention type: Drug
intervention name: Placebo to fluticasone/salmeterol
description: Placebo to fluticasone/salmeterol with Accuhaler
arm group label: QVA149
other name: Comparator: fluticasone/salmeterol
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: Argentina
country: Chile
country: China
country: Taiwan
country: Brazil
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Fluticasone
mesh term: Xhance
mesh term: Glycopyrrolate
mesh term: Salmeterol Xinafoate
mesh term: Fluticasone-Salmeterol Drug Combination
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 