<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/NCT01682863</url>
  </required_header>
  <id_info>
    <org_study_id>CQVA149A2340</org_study_id>
    <secondary_id>2012-001998-93</secondary_id>
    <nct_id>NCT01682863</nct_id>
  </id_info>
  <brief_title>A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation</brief_title>
  <official_title>A Multi-centre Randomized Double Blind 52-week Study to Assess the Safety of QVA149 Compared to QAB149 in Patients With COPD Who Have Moderate to Severe Airflow Limitation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is to assess the safety and tolerability of two different doses of QVA149 and&#xD;
      QAB149 in patients with moderate to severe airflow limitation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">June 2014</completion_date>
  <primary_completion_date type="Actual">June 2014</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Patients With Adverse Events, Serious Adverse Events, and Death</measure>
    <time_frame>56 weeks</time_frame>
    <description>The overall rate of adverse events reported from initiation through 30 days post last dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Premature Discontinuation of Treatment</measure>
    <time_frame>56 weeks</time_frame>
    <description>methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pre-dose Trough FEV1</measure>
    <time_frame>Day 29, 57,, 85, 141, 197, 253, 309 and 365</time_frame>
    <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in 1 Hour Post-dose FEV1 Measurements</measure>
    <time_frame>Day 1, 29, 57, 85, 141, 197, 253, 309, and 365</time_frame>
    <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in FVC Measurement at All Post-baseline Time Points</measure>
    <time_frame>Day1, 29, 57, 85, 141, 197, 253, 309, and 365</time_frame>
    <description>Pulmonary function assessments were performed using centralized spirometry according to international standards.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation</measure>
    <time_frame>52 weeks</time_frame>
    <description>Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Total Daily Symptom Scores</measure>
    <time_frame>52 weeks</time_frame>
    <description>The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period</measure>
    <time_frame>52 weeks</time_frame>
    <description>Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">614</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>QVA149 dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>QVA149 27.5/12.5 μg capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>QVA149 dose 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>QVA149 27.5/25 μg capsules</description>
  </arm_group>
  <arm_group>
    <arm_group_label>QAB149</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>QAB149 75 μg capsules</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QVA149</intervention_name>
    <description>QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI</description>
    <arm_group_label>QVA149 dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QVA149</intervention_name>
    <description>QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI</description>
    <arm_group_label>QVA149 dose 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>QAB149</intervention_name>
    <description>QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI</description>
    <arm_group_label>QAB149</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>To mimic QAB149</description>
    <arm_group_label>QAB149</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and female adults aged ≥40 years&#xD;
&#xD;
          -  Patients with stable COPD according to GOLD strategy (GOLD 2011).&#xD;
&#xD;
          -  Patients with airflow limitation indicated by a post-bronchodilator FEV1 ≥ 30% and&#xD;
             &lt;80% of the predicted normal, and a post-bronchodilator FEV1/FVC &lt; 0.70.&#xD;
&#xD;
          -  Current or ex-smokers who have a smoking history of at least 10 pack years.&#xD;
&#xD;
          -  Patients with an mMRC ≥ grade 2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of long QT syndrome or prolonged QTc&#xD;
&#xD;
          -  Patients who have had a COPD exacerbation that required treatment with antibiotics&#xD;
             and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to Visit&#xD;
             1.&#xD;
&#xD;
          -  Patients with Type I or uncontrolled Type II diabetes&#xD;
&#xD;
          -  Patients with a history of asthma or have concomitant pulmonary disease&#xD;
&#xD;
          -  Patients with paroxysmal (e.g. intermittent) atrial fibrillation. Only patients with&#xD;
             persistent atrial fibrillation and controlled with a rate control strategy for at&#xD;
             least six months could be eligible&#xD;
&#xD;
          -  Patients who have clinically significant renal, cardiovascular, neurological,&#xD;
             endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological&#xD;
             abnormalities which could interfere with the assessment of safety&#xD;
&#xD;
          -  Other protocol defined inclusion/exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vestavia</city>
        <state>Alabama</state>
        <zip>35216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Huntington Beach</city>
        <state>California</state>
        <zip>92647</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lakewood</city>
        <state>California</state>
        <zip>90712-151</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stockton</city>
        <state>California</state>
        <zip>95207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Walnut Creek</city>
        <state>California</state>
        <zip>94598</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96814</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lombard</city>
        <state>Illinois</state>
        <zip>60148</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>O'Fallon</city>
        <state>Illinois</state>
        <zip>62269</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Peoria</city>
        <state>Illinois</state>
        <zip>61602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Evansville</city>
        <state>Indiana</state>
        <zip>47712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ames</city>
        <state>Iowa</state>
        <zip>50010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Waterloo</city>
        <state>Iowa</state>
        <zip>50702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bowling Green</city>
        <state>Kentucky</state>
        <zip>42101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Slidell</city>
        <state>Louisiana</state>
        <zip>70458</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bangor</city>
        <state>Maine</state>
        <zip>04401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Livonia</city>
        <state>Michigan</state>
        <zip>48152</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jackson</city>
        <state>Mississippi</state>
        <zip>39209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Picayune</city>
        <state>Mississippi</state>
        <zip>39466</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Charles</city>
        <state>Missouri</state>
        <zip>63301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Missoula</city>
        <state>Montana</state>
        <zip>59804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68131</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <zip>89014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14618</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45459</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dublin</city>
        <state>Ohio</state>
        <zip>43016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504-8741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Knoxville</city>
        <state>Tennessee</state>
        <zip>37912</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Corsicana</city>
        <state>Texas</state>
        <zip>75110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ft. Worth</city>
        <state>Texas</state>
        <zip>76104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lufkin</city>
        <state>Texas</state>
        <zip>75904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>McKinney</city>
        <state>Texas</state>
        <zip>75069</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Abingdon</city>
        <state>Virginia</state>
        <zip>24210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Midlothian</city>
        <state>Virginia</state>
        <zip>23114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Newport News</city>
        <state>Virginia</state>
        <zip>23606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ruse</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Varna</city>
        <zip>9010</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Helsinki</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>HUS</city>
        <zip>00029</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pori</city>
        <zip>FIN-28500</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Turku</city>
        <zip>20521</zip>
        <country>Finland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <zip>1046</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Budapest</city>
        <zip>1125</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gyor</city>
        <zip>9024</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mako</city>
        <zip>6900</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Nyiregyhaza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pecs</city>
        <zip>7635</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Szazhalombatta</city>
        <zip>2440</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Szolnok</city>
        <zip>H-5000</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Torokbalint</city>
        <zip>2045</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barceloneta</city>
        <zip>00617</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Juan</city>
        <zip>00909</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Juan</city>
        <zip>00918</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <state>District 1</state>
        <zip>10457</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <state>District 1</state>
        <zip>11475</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <state>District 3</state>
        <zip>030303</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <state>District 3</state>
        <zip>030317</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Constanta</city>
        <state>Jud. Constanta</state>
        <zip>900002</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Iasi</city>
        <state>Jud. Iasi</state>
        <zip>700115</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brasov</city>
        <zip>500281</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucharest</city>
        <zip>060011</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bucuresti</city>
        <zip>50554</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cluj-Napoca</city>
        <zip>400371</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Granada</city>
        <state>Andalucia</state>
        <zip>18014</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Málaga</city>
        <state>Andalucia</state>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Badalona</city>
        <state>Cataluña</state>
        <zip>08914</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Cataluña</state>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Canet de Mar</city>
        <state>Cataluña</state>
        <zip>08360</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Centelles</city>
        <state>Cataluña</state>
        <zip>08540</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tarragona</city>
        <state>Cataluña</state>
        <zip>43350</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Valencia</city>
        <state>Comunidad Valenciana</state>
        <zip>46015</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Finland</country>
    <country>Hungary</country>
    <country>Puerto Rico</country>
    <country>Romania</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>India</country>
  </removed_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 7, 2012</study_first_submitted>
  <study_first_submitted_qc>September 7, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2012</study_first_posted>
  <results_first_submitted>June 22, 2015</results_first_submitted>
  <results_first_submitted_qc>February 29, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 30, 2016</results_first_posted>
  <last_update_submitted>February 29, 2016</last_update_submitted>
  <last_update_submitted_qc>February 29, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 30, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD, QAB149, QVA149, indacaterol maleate, gylcopyrronium bromide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Patients were randomized to each treatment arm in 1:1:1 ratio.</recruitment_details>
      <pre_assignment_details>Six hundred fifteen patients were randomized. One patient was randomized but did not receive treatment due to an adverse event. In the safety set, patients were analyzed according to the treatment received. Therefore, protocol enrollment and analysis set was 614 but the participant flow was 615</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>QVA149 27.5/12.5 ug Bid</title>
        </group>
        <group group_id="P2">
          <title>QVA149 27.5/25 ug Bid</title>
        </group>
        <group group_id="P3">
          <title>QAB149 75 ug od</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="204"/>
                <participants group_id="P2" count="204"/>
                <participants group_id="P3" count="207"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Set</title>
              <participants_list>
                <participants group_id="P1" count="204"/>
                <participants group_id="P2" count="204"/>
                <participants group_id="P3" count="206"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="204">included all randomized patients who received at least one dose of study medication</participants>
                <participants group_id="P2" count="204"/>
                <participants group_id="P3" count="206"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Randomized Set</title>
              <participants_list>
                <participants group_id="P1" count="204"/>
                <participants group_id="P2" count="204"/>
                <participants group_id="P3" count="207">1 randomized patient was not treated; experienced an AE prior to receiving any study drug</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="177"/>
                <participants group_id="P2" count="187"/>
                <participants group_id="P3" count="183"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="12"/>
                <participants group_id="P3" count="10"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Technical problems</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Patients were analyzed according to the treatment they were assigned to at randomization.</population>
      <group_list>
        <group group_id="B1">
          <title>QVA149 27.5/12.5 ug Bid</title>
        </group>
        <group group_id="B2">
          <title>QVA149 27.5/25 ug Bid</title>
        </group>
        <group group_id="B3">
          <title>QAB149 75 ug od</title>
        </group>
        <group group_id="B4">
          <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="204"/>
            <count group_id="B2" value="204"/>
            <count group_id="B3" value="207"/>
            <count group_id="B4" value="615"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.0" spread="7.90"/>
                    <measurement group_id="B2" value="63.9" spread="8.50"/>
                    <measurement group_id="B3" value="62.8" spread="8.52"/>
                    <measurement group_id="B4" value="63.6" spread="8.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="81"/>
                    <measurement group_id="B3" value="58"/>
                    <measurement group_id="B4" value="212"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="131"/>
                    <measurement group_id="B2" value="123"/>
                    <measurement group_id="B3" value="149"/>
                    <measurement group_id="B4" value="403"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Patients With Adverse Events, Serious Adverse Events, and Death</title>
        <description>The overall rate of adverse events reported from initiation through 30 days post last dose.</description>
        <time_frame>56 weeks</time_frame>
        <population>The Safety set:all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. The statement that a patient had no AEs also constituted a safety assessment. Only deaths occurring on treatment + 30 days after end of treatment were included.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Adverse Events, Serious Adverse Events, and Death</title>
          <description>The overall rate of adverse events reported from initiation through 30 days post last dose.</description>
          <population>The Safety set:all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received. The statement that a patient had no AEs also constituted a safety assessment. Only deaths occurring on treatment + 30 days after end of treatment were included.</population>
          <units>Number of Patients</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="204"/>
                <count group_id="O2" value="204"/>
                <count group_id="O3" value="206"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Patients with at least one SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="25"/>
                    <measurement group_id="O3" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Patients with at least one AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139"/>
                    <measurement group_id="O2" value="142"/>
                    <measurement group_id="O3" value="139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="3"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Premature Discontinuation of Treatment</title>
        <description>methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl</description>
        <time_frame>56 weeks</time_frame>
        <population>The Safety set consisted of all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Time to Premature Discontinuation of Treatment</title>
          <description>methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl</description>
          <population>The Safety set consisted of all patients that received at least one dose of study medication and had at least one post-baseline safety assessment. Patients were analyzed according to treatment received.</population>
          <units>Days</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="204"/>
                <count group_id="O2" value="204"/>
                <count group_id="O3" value="206"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="384.0" spread="0.164" lower_limit="384.0" upper_limit="NA">NA- Not estimable</measurement>
                    <measurement group_id="O2" value="NA" spread="0.164" lower_limit="NA" upper_limit="NA">NA- Not estimable</measurement>
                    <measurement group_id="O3" value="NA" spread="0.166" lower_limit="NA" upper_limit="NA">NA- Not estimable</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pre-dose Trough FEV1</title>
        <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
        <time_frame>Day 29, 57,, 85, 141, 197, 253, 309 and 365</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pre-dose Trough FEV1</title>
          <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</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="192"/>
                <count group_id="O2" value="196"/>
                <count group_id="O3" value="199"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.164" spread="0.0144"/>
                    <measurement group_id="O2" value="0.194" spread="0.0143"/>
                    <measurement group_id="O3" value="0.109" spread="0.0143"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.178" spread="0.0151"/>
                    <measurement group_id="O2" value="0.199" spread="0.0149"/>
                    <measurement group_id="O3" value="0.107" spread="0.0149"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.166" spread="0.0158"/>
                    <measurement group_id="O2" value="0.201" spread="0.0157"/>
                    <measurement group_id="O3" value="0.095" spread="0.0157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.174" spread="0.0173"/>
                    <measurement group_id="O2" value="0.198" spread="0.0170"/>
                    <measurement group_id="O3" value="0.087" spread="0.0171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.138" spread="0.0167"/>
                    <measurement group_id="O2" value="0.181" spread="0.0165"/>
                    <measurement group_id="O3" value="0.079" spread="0.0166"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.142" spread="0.0168"/>
                    <measurement group_id="O2" value="0.153" spread="0.0165"/>
                    <measurement group_id="O3" value="0.074" spread="0.0167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.096" spread="0.0162"/>
                    <measurement group_id="O2" value="0.123" spread="0.0161"/>
                    <measurement group_id="O3" value="0.050" spread="0.0162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.116" spread="0.0169"/>
                    <measurement group_id="O2" value="0.116" spread="0.0167"/>
                    <measurement group_id="O3" value="0.037" spread="0.0169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in 1 Hour Post-dose FEV1 Measurements</title>
        <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
        <time_frame>Day 1, 29, 57, 85, 141, 197, 253, 309, and 365</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in 1 Hour Post-dose FEV1 Measurements</title>
          <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</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="200"/>
                <count group_id="O2" value="202"/>
                <count group_id="O3" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.166" spread="0.0088"/>
                    <measurement group_id="O2" value="0.178" spread="0.0088"/>
                    <measurement group_id="O3" value="0.122" spread="0.0089"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.257" spread="0.0152"/>
                    <measurement group_id="O2" value="0.287" spread="0.0151"/>
                    <measurement group_id="O3" value="0.173" spread="0.0151"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.267" spread="0.0157"/>
                    <measurement group_id="O2" value="0.302" spread="0.0155"/>
                    <measurement group_id="O3" value="0.173" spread="0.0154"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.269" spread="0.0164"/>
                    <measurement group_id="O2" value="0.301" spread="0.0162"/>
                    <measurement group_id="O3" value="0.170" spread="0.0162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.268" spread="0.0182"/>
                    <measurement group_id="O2" value="0.288" spread="0.0179"/>
                    <measurement group_id="O3" value="0.170" spread="0.0181"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.229" spread="0.0178"/>
                    <measurement group_id="O2" value="0.278" spread="0.0175"/>
                    <measurement group_id="O3" value="0.157" spread="0.0177"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.231" spread="0.0178"/>
                    <measurement group_id="O2" value="0.240" spread="0.0175"/>
                    <measurement group_id="O3" value="0.140" spread="0.0176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.199" spread="0.0170"/>
                    <measurement group_id="O2" value="0.222" spread="0.0169"/>
                    <measurement group_id="O3" value="0.125" spread="0.0170"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.212" spread="0.0175"/>
                    <measurement group_id="O2" value="0.221" spread="0.0173"/>
                    <measurement group_id="O3" value="0.104" spread="0.0174"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in FVC Measurement at All Post-baseline Time Points</title>
        <description>Pulmonary function assessments were performed using centralized spirometry according to international standards.</description>
        <time_frame>Day1, 29, 57, 85, 141, 197, 253, 309, and 365</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in FVC Measurement at All Post-baseline Time Points</title>
          <description>Pulmonary function assessments were performed using centralized spirometry according to international standards.</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</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="200"/>
                <count group_id="O2" value="202"/>
                <count group_id="O3" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.316" spread="0.0201"/>
                    <measurement group_id="O2" value="0.349" spread="0.0200"/>
                    <measurement group_id="O3" value="0.248" spread="0.0203"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.375" spread="0.0274"/>
                    <measurement group_id="O2" value="0.440" spread="0.0271"/>
                    <measurement group_id="O3" value="0.280" spread="0.0272"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.390" spread="0.0274"/>
                    <measurement group_id="O2" value="0.439" spread="0.0271"/>
                    <measurement group_id="O3" value="0.279" spread="0.0271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.388" spread="0.0287"/>
                    <measurement group_id="O2" value="0.432" spread="0.0283"/>
                    <measurement group_id="O3" value="0.268" spread="0.0284"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.382" spread="0.0297"/>
                    <measurement group_id="O2" value="0.403" spread="0.0292"/>
                    <measurement group_id="O3" value="0.235" spread="0.0295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.313" spread="0.0288"/>
                    <measurement group_id="O2" value="0.400" spread="0.0284"/>
                    <measurement group_id="O3" value="0.220" spread="0.0288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.310" spread="0.0303"/>
                    <measurement group_id="O2" value="0.365" spread="0.0298"/>
                    <measurement group_id="O3" value="0.205" spread="0.0301"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.272" spread="0.0284"/>
                    <measurement group_id="O2" value="0.334" spread="0.0281"/>
                    <measurement group_id="O3" value="0.185" spread="0.0285"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.312" spread="0.0286"/>
                    <measurement group_id="O2" value="0.323" spread="0.0282"/>
                    <measurement group_id="O3" value="0.139" spread="0.0286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation</title>
        <description>Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)</description>
        <time_frame>52 weeks</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation</title>
          <description>Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="204"/>
                <count group_id="O2" value="204"/>
                <count group_id="O3" value="206"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.5"/>
                    <measurement group_id="O2" value="24.9"/>
                    <measurement group_id="O3" value="27.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Total Daily Symptom Scores</title>
        <description>The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.</description>
        <time_frame>52 weeks</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Total Daily Symptom Scores</title>
          <description>The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
          <units>Score 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="198"/>
                <count group_id="O2" value="199"/>
                <count group_id="O3" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.57" spread="0.133"/>
                    <measurement group_id="O2" value="-1.56" spread="0.133"/>
                    <measurement group_id="O3" value="-1.31" spread="0.135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period</title>
        <description>Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.</description>
        <time_frame>52 weeks</time_frame>
        <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
        <group_list>
          <group group_id="O1">
            <title>QVA149 27.5/12.5 ug Bid</title>
          </group>
          <group group_id="O2">
            <title>QVA149 27.5/25 ug Bid</title>
          </group>
          <group group_id="O3">
            <title>QAB149 75 ug od</title>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period</title>
          <description>Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.</description>
          <population>The Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Participants, who had both baseline and week 52 values, were included in the analysis. Patients were analyzed according to the treatment to which they were randomized.</population>
          <units>Number of puffs</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="198"/>
                <count group_id="O2" value="199"/>
                <count group_id="O3" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.89" spread="0.164"/>
                    <measurement group_id="O2" value="-1.62" spread="0.164"/>
                    <measurement group_id="O3" value="-1.73" spread="0.166"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>QVA149 27.5/12.5 ug Bid</title>
        </group>
        <group group_id="E2">
          <title>QVA149 27.5/25 ug Bid</title>
        </group>
        <group group_id="E3">
          <title>QAB75</title>
          <description>QVA149 27.5/25 μg capsules</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="26" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="25" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="24" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>ANAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </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="2" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ANGINA UNSTABLE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ATRIAL FLUTTER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ATRIOVENTRICULAR BLOCK SECOND DEGREE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>BRADYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CARDIAC FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CARDIAC FAILURE ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CARDIAC TAMPONADE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CARDIO-RESPIRATORY ARREST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CARDIOGENIC SHOCK</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY OCCLUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>MYOCARDIAL ISCHAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PERICARDIAL EFFUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SILENT MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Congenital, familial and genetic disorders</title>
            <event_list>
              <event>
                <sub_title>ASPLENIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HIATUS HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>INGUINAL HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>INGUINAL HERNIA STRANGULATED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>INTESTINAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>LARGE INTESTINE PERFORATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ORAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FACIAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>ARTHRITIS INFECTIVE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>BRONCHOPNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>DIVERTICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>ERYSIPELAS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>H1N1 INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>LOWER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>LUNG INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>MENINGITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PYELONEPHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PYELONEPHRITIS ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION BACTERIAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>BRAIN HERNIATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RIB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SKULL FRACTURED BASE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SUBDURAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>DEHYDRATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HYPOGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>INTERVERTEBRAL DISC PROTRUSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>ADENOCARCINOMA OF COLON</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>BONE CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>COLON CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>KAPOSI'S SARCOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>LUNG NEOPLASM MALIGNANT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>METASTASES TO LUNG</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>METASTASES TO PERITONEUM</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>METASTASES TO SPINE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>NON-SMALL CELL LUNG CANCER STAGE IV</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PROSTATE CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RENAL CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SQUAMOUS CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SQUAMOUS CELL CARCINOMA OF LUNG</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>BRAIN OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>CEREBRAL ISCHAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SUBARACHNOID HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>TRANSIENT ISCHAEMIC ATTACK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>PANIC ATTACK</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SUICIDE ATTEMPT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>RENAL FAILURE ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RENAL IMPAIRMENT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>BENIGN PROSTATIC HYPERPLASIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </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="8" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HAEMOTHORAX</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PLEURAL EFFUSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PNEUMONIA ASPIRATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PULMONARY MASS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>AORTIC DISSECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HAEMATOMA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </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="118" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="117" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="112" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>GASTROOESOPHAGEAL REFLUX DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>LOWER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="19" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="22" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RESPIRATORY TRACT INFECTION VIRAL</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>RHINITIS</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION BACTERIAL</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="13" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>CONTUSION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>MUSCLE SPASMS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="206"/>
              </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="70" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="64" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="71" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>PRODUCTIVE COUGH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>PRURITUS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>SKIN LESION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="206"/>
              </event>
              <event>
                <sub_title>HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="204"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="204"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="206"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>862-778-8300</phone>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01682863
org study id: CQVA149A2340
secondary id: 2012-001998-93
nct id: NCT01682863
lead sponsor: 
has dmc: Yes
This study is to assess the safety and tolerability of two different doses of QVA149 and
      QAB149 in patients with moderate to severe airflow limitation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Patients With Adverse Events, Serious Adverse Events, and Death
time frame: 56 weeks
description: The overall rate of adverse events reported from initiation through 30 days post last dose.
measure: Time to Premature Discontinuation of Treatment
time frame: 56 weeks
description: methodTime to premature treatment discontinuation for each treatment group was displayed using a Kaplan-Meier curve. The date of last dose of study medication was considered as the event date and also as the censoring date for those patients who did not discontinue treatment earl
measure: Change From Baseline in Pre-dose Trough FEV1
time frame: Day 29, 57,, 85, 141, 197, 253, 309 and 365
description: Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.
measure: Change From Baseline in 1 Hour Post-dose FEV1 Measurements
time frame: Day 1, 29, 57, 85, 141, 197, 253, 309, and 365
description: Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction.
measure: Change From Baseline in FVC Measurement at All Post-baseline Time Points
time frame: Day1, 29, 57, 85, 141, 197, 253, 309, and 365
description: Pulmonary function assessments were performed using centralized spirometry according to international standards.
measure: Percentage of Participants Experiencing Moderate or Severe COPD Exacerbation
time frame: 52 weeks
description: Percentage of participants experiencing moderate or severe Chronic Obstructive Pulmonary Disease (COPD)
measure: Change From Baseline in Mean Total Daily Symptom Scores
time frame: 52 weeks
description: The participant recorded symptom scores twice daily in the eDiary. The daily clinical symptoms included: cough, wheezing, shortness of breath, sputum volume, sputum color, and night time awakening. The range of scores for each assessment is 0 to 3 where 0 indications No symptom and 3 indicates a Severe symptom. The maximum daytime total score is 27 and the maximum nighttime total score is 27. The total daily symptom score is obtained by adding the scores for the morning and evening symptoms for each day. The maximum possible total daily score is 54. A negative change from baseline indicated improvement.
measure: Change From Baseline in the Daily Number of Puffs of Rescue Medication Over the 52 Week Period
time frame: 52 weeks
description: Participants completed an electronic diary (eDiary) twice daily at the same time in the morning and evening to record the number of puffs of rescue medication taken in the previous 12 hours.
arm group label: QVA149 dose 1
arm group type: Experimental
description: QVA149 27.5/12.5 μg capsules
arm group label: QVA149 dose 2
arm group type: Experimental
description: QVA149 27.5/25 μg capsules
arm group label: QAB149
arm group type: Active Comparator
description: QAB149 75 μg capsules
intervention type: Drug
intervention name: QVA149
description: QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
arm group label: QVA149 dose 1
intervention type: Drug
intervention name: QVA149
description: QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept1 SDDPI
arm group label: QVA149 dose 2
intervention type: Drug
intervention name: QAB149
description: QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept1 SDDPI
arm group label: QAB149
intervention type: Drug
intervention name: Placebo
description: To mimic QAB149
arm group label: QAB149
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
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country: Bulgaria
country: Finland
country: Hungary
country: Puerto Rico
country: Romania
country: Spain
country: United States
country: India
responsible party type: Sponsor
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 