<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/NCT01697696</url>
  </required_header>
  <id_info>
    <org_study_id>CNVA237A2319</org_study_id>
    <secondary_id>2012-002728-34</secondary_id>
    <nct_id>NCT01697696</nct_id>
  </id_info>
  <brief_title>Long Term Safety Study of NVA237 vs QAB149 in COPD Patients</brief_title>
  <official_title>A Multi-center, Randomized, Double-blind, 52-week Study to Assess the Safety of NVA237 Compared to QAB149 in Patients With Chronic Obstructive Pulmonary Disease (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>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to provide long term safety data of NVA237. This study will&#xD;
      assess the safety and tolerability of a single dose strength of NVA237.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 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>Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate</measure>
    <time_frame>52 weeks</time_frame>
    <description>Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to Treatment Discontinuation</measure>
    <time_frame>52 Weeks</time_frame>
    <description>Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52</measure>
    <time_frame>-45 min and -15 minutes baseline and at Week 52</time_frame>
    <description>Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints</measure>
    <time_frame>-45 min and -15 minutes baseline and at Week 52</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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints</measure>
    <time_frame>-45 min and -15 minutes baseline and at Week 52</time_frame>
    <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in COPD Symptoms</measure>
    <time_frame>52 weeks</time_frame>
    <description>The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in COPD Symptoms</measure>
    <time_frame>52 weeks</time_frame>
    <description>Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Daily Number of Puffs of Rescue Medication</measure>
    <time_frame>52 weeks</time_frame>
    <description>The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First COPD Exacerbation (Moderate or Severe).</measure>
    <time_frame>52 weeks</time_frame>
    <description>COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">511</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease (COPD)</condition>
  <arm_group>
    <arm_group_label>NVA237 dose 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NVA237 dose 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Long-acting beta 2-agonist (LABA)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>QAB149</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVA237</intervention_name>
    <description>NVA237 will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI</description>
    <arm_group_label>NVA237 dose 1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Long-acting beta 2-agonist (LABA)</intervention_name>
    <description>QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI</description>
    <arm_group_label>Long-acting beta 2-agonist (LABA)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo to match QAB149</description>
    <arm_group_label>Long-acting beta 2-agonist (LABA)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female patients with COPD according to GOLD 2011 who have signed informed&#xD;
             consent.&#xD;
&#xD;
          2. Patients with airflow limitation of 30-80% post-bronchodilator FEV1 at run-in.&#xD;
&#xD;
          3. Current or ex-smokers with a smoking history of at least 10 pack years&#xD;
&#xD;
          4. Patients with a mMRC score of at least 2 at run-in.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients contraindicated for muscarinic antagonist agents and beta-2 agonists&#xD;
&#xD;
          2. Patients with a history of malignancy of any organ system, treated or untreated,&#xD;
             within the last five years&#xD;
&#xD;
          3. Patients with narrow-angle glaucoma, BPH or bladder-neck obstruction or&#xD;
             moderate-severe renal impairment or urinary retention&#xD;
&#xD;
          4. Patients who had a COPD exacerbation within 6 weeks prior to screening.&#xD;
&#xD;
          5. Patients requiring long term oxygen therapy prescribed for more than 12 hr per day.&#xD;
&#xD;
          6. Patients with a history of asthma.&#xD;
&#xD;
          7. Patients with an onset of respiratory symptoms, including COPD diagnosis, prior to 40&#xD;
             years of age.&#xD;
&#xD;
          8. Patients with a blood eosinophil count of greater than 600 mm/3 during run-in&#xD;
&#xD;
          9. Patients with concomitant pulmonary disease&#xD;
&#xD;
         10. Patients with a history of certain cardiovascular co-morbid conditions&#xD;
&#xD;
         11. Patients with a diagnosis of alpha-1 anti-trypsin deficiency&#xD;
&#xD;
         12. Patients with active pulmonary tuberculosis&#xD;
&#xD;
         13. Patients in the active phase of a pulmonary rehabilitation programme&#xD;
&#xD;
         14. Other protocol-defined inclusion / exclusion criteria may apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gulf Shores</city>
        <state>Alabama</state>
        <zip>36547</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <zip>36608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80528</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Glastonbury</city>
        <state>Connecticut</state>
        <zip>06033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <zip>06902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Waterbury</city>
        <state>Connecticut</state>
        <zip>06708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33172</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33175</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oakland Park</city>
        <state>Florida</state>
        <zip>33334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Couer D'Alene</city>
        <state>Idaho</state>
        <zip>83814</zip>
        <country>United States</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Newburgh</city>
        <state>Indiana</state>
        <zip>47630</zip>
        <country>United States</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Florence</city>
        <state>Kentucky</state>
        <zip>41042</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Madisonville</city>
        <state>Kentucky</state>
        <zip>42431</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Opelousas</city>
        <state>Louisiana</state>
        <zip>70570</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Biddeford</city>
        <state>Maine</state>
        <zip>04005</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Worchester</city>
        <state>Massachusetts</state>
        <zip>01608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55402</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>Fremont</city>
        <state>Nebraska</state>
        <zip>68025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68134</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>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Calabash</city>
        <state>North Carolina</state>
        <zip>28467</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tabor City</city>
        <state>North Carolina</state>
        <zip>28463</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Marion</city>
        <state>Ohio</state>
        <zip>43302</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Zanesville</city>
        <state>Ohio</state>
        <zip>43701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Eugene</city>
        <state>Oregon</state>
        <zip>97404-3233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19140</zip>
        <country>United States</country>
      </address>
    </facility>
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  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Warwick</city>
        <state>Rhode Island</state>
        <zip>02886</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29412</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>N. Myrtle Beach</city>
        <state>South Carolina</state>
        <zip>29582</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boerne</city>
        <state>Texas</state>
        <zip>78006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <zip>79902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77043</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Kingwood</city>
        <state>Texas</state>
        <zip>77339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>White River Junction</city>
        <state>Vermont</state>
        <zip>05009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Burke</city>
        <state>Virginia</state>
        <zip>22015</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fredericksburg</city>
        <state>Virginia</state>
        <zip>22401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Manassas</city>
        <state>Virginia</state>
        <zip>20110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oregon</city>
        <state>Wisconsin</state>
        <zip>53575</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2016</verification_date>
  <study_first_submitted>September 28, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 2, 2012</study_first_posted>
  <results_first_submitted>November 10, 2015</results_first_submitted>
  <results_first_submitted_qc>February 17, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 16, 2016</results_first_posted>
  <last_update_submitted>February 17, 2016</last_update_submitted>
  <last_update_submitted_qc>February 17, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 16, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD, NVA237, QAB149, glycopyrronium bromide</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>NVA237</title>
          <description>12.5 μg twice-daily</description>
        </group>
        <group group_id="P2">
          <title>QAB149</title>
          <description>75 μg once-daily</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="254"/>
                <participants group_id="P2" count="257"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Set</title>
              <participants_list>
                <participants group_id="P1" count="251"/>
                <participants group_id="P2" count="256">Safety set included a patient that was treated, but not randomized</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="251"/>
                <participants group_id="P2" count="255"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="207"/>
                <participants group_id="P2" count="210"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study terminated by sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
              </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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="35"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The Safety set included all patients that received at least one dose of study drug and had at least one-post baseline assessment . Subjects were analyzed according to the treatment they received (if a subject incorrectly took more than one treatment, the subject was analyzed according to the treatment they were randomized to).</population>
      <group_list>
        <group group_id="B1">
          <title>NVA237</title>
          <description>12.5 μg twice-daily</description>
        </group>
        <group group_id="B2">
          <title>QAB149</title>
          <description>75 μg once-daily</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="251"/>
            <count group_id="B2" value="256"/>
            <count group_id="B3" value="507"/>
          </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="63.3" spread="9.15"/>
                    <measurement group_id="B2" value="63.2" spread="8.91"/>
                    <measurement group_id="B3" value="63.3" spread="9.02"/>
                  </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="110"/>
                    <measurement group_id="B2" value="107"/>
                    <measurement group_id="B3" value="217"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="141"/>
                    <measurement group_id="B2" value="149"/>
                    <measurement group_id="B3" value="290"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate</title>
        <description>Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.</description>
        <time_frame>52 weeks</time_frame>
        <population>Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this analysis</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate</title>
          <description>Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.</description>
          <population>Safety population - all patients who received at least one dose of study drug whether or not they were randomized. Only patients with safety assessments were included in this 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="251"/>
                <count group_id="O2" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.3"/>
                    <measurement group_id="O2" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Treatment Discontinuation</title>
        <description>Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems</description>
        <time_frame>52 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>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Treatment Discontinuation</title>
          <description>Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems</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="251"/>
                <count group_id="O2" value="256"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">NA - Insufficient number of participants with events</measurement>
                    <measurement group_id="O2" value="388" lower_limit="388" upper_limit="NA">NA - Insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52</title>
        <description>Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.</description>
        <time_frame>-45 min and -15 minutes baseline and at Week 52</time_frame>
        <population>The Full Analysis set (FAS) included patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52</title>
          <description>Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.</description>
          <population>The Full Analysis set (FAS) included patients who received at least one dose of study medication. Patients were analyzed according to the treatment to which they were randomized. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</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="229"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.056" spread="0.0211"/>
                    <measurement group_id="O2" value="0.060" spread="0.0213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints</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.</description>
        <time_frame>-45 min and -15 minutes baseline and at Week 52</time_frame>
        <population>The Full Analysis set (FAS). At each day/time point, only subjects with a value at both baseline and the respective day/time point are included. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints</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.</description>
          <population>The Full Analysis set (FAS). At each day/time point, only subjects with a value at both baseline and the respective day/time point are included. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 29/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.104" spread="0.1848"/>
                    <measurement group_id="O2" value="0.118" spread="0.2093"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.1872"/>
                    <measurement group_id="O2" value="0.138" spread="0.2061"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.098" spread="0.2017"/>
                    <measurement group_id="O2" value="0.101" spread="0.2091"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.120" spread="0.2025"/>
                    <measurement group_id="O2" value="0.107" spread="0.2111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.105" spread="0.2410"/>
                    <measurement group_id="O2" value="0.085" spread="0.2255"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.111" spread="0.2137"/>
                    <measurement group_id="O2" value="0.099" spread="0.2328"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.071" spread="0.2168"/>
                    <measurement group_id="O2" value="0.089" spread="0.2595"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.096" spread="0.2060"/>
                    <measurement group_id="O2" value="0.108" spread="0.2670"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.071" spread="0.2370"/>
                    <measurement group_id="O2" value="0.082" spread="0.2637"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.073" spread="0.2150"/>
                    <measurement group_id="O2" value="0.090" spread="0.2827"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.092" spread="0.2774"/>
                    <measurement group_id="O2" value="0.087" spread="0.2679"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.094" spread="0.2100"/>
                    <measurement group_id="O2" value="0.103" spread="0.2659"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.068" spread="0.2850"/>
                    <measurement group_id="O2" value="0.094" spread="0.2594"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.088" spread="0.2845"/>
                    <measurement group_id="O2" value="0.112" spread="0.2638"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.057" spread="0.2541"/>
                    <measurement group_id="O2" value="0.088" spread="0.2521"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.087" spread="0.2592"/>
                    <measurement group_id="O2" value="0.090" spread="0.2627"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints</title>
        <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.</description>
        <time_frame>-45 min and -15 minutes baseline and at Week 52</time_frame>
        <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints</title>
          <description>Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.</description>
          <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants with baseline and specific post baseline time points were included in the analysis for that time point.</population>
          <units>Liters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="229"/>
                <count group_id="O2" value="227"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 29/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.191" spread="0.3433"/>
                    <measurement group_id="O2" value="0.170" spread="0.3536"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 29/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.217" spread="0.3440"/>
                    <measurement group_id="O2" value="0.194" spread="0.3495"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.168" spread="0.3501"/>
                    <measurement group_id="O2" value="0.140" spread="0.3655"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 57/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.210" spread="0.3414"/>
                    <measurement group_id="O2" value="0.178" spread="0.3610"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.171" spread="0.3907"/>
                    <measurement group_id="O2" value="0.094" spread="0.3711"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 85/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.188" spread="0.3875"/>
                    <measurement group_id="O2" value="0.118" spread="0.3823"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.159" spread="0.3742"/>
                    <measurement group_id="O2" value="0.112" spread="0.3822"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 141/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.182" spread="0.3706"/>
                    <measurement group_id="O2" value="0.141" spread="0.4068"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.140" spread="0.3879"/>
                    <measurement group_id="O2" value="0.075" spread="0.4043"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 197/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.133" spread="0.3992"/>
                    <measurement group_id="O2" value="0.083" spread="0.4183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.167" spread="0.4567"/>
                    <measurement group_id="O2" value="0.100" spread="0.4219"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 253/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.153" spread="0.3703"/>
                    <measurement group_id="O2" value="0.125" spread="0.3984"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.120" spread="0.4539"/>
                    <measurement group_id="O2" value="0.094" spread="0.4122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 309/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.149" spread="0.4451"/>
                    <measurement group_id="O2" value="0.114" spread="0.4207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365/-45min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.116" spread="0.4053"/>
                    <measurement group_id="O2" value="0.109" spread="0.4426"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 365/-15min</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.143" spread="0.3970"/>
                    <measurement group_id="O2" value="0.097" spread="0.4171"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in COPD Symptoms</title>
        <description>The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.</description>
        <time_frame>52 weeks</time_frame>
        <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.&quot;</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in COPD Symptoms</title>
          <description>The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.</description>
          <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.&quot;</population>
          <units>scores 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="251"/>
                <count group_id="O2" value="255"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Daily total symptom score (n=231, 227)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.18" spread="0.137"/>
                    <measurement group_id="O2" value="-1.47" spread="0.137"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daytime total symptom score (n=221, 220)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.95" spread="0.129"/>
                    <measurement group_id="O2" value="-1.14" spread="0.129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nighttime total symptom score (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.11" spread="0.126"/>
                    <measurement group_id="O2" value="-1.25" spread="0.128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in COPD Symptoms</title>
        <description>Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.</description>
        <time_frame>52 weeks</time_frame>
        <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in COPD Symptoms</title>
          <description>Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.</description>
          <population>Full Analysis set (FAS) included all randomized patients who received at least one dose of study medication. Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</population>
          <units>Percentage of days / nights</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="251"/>
                <count group_id="O2" value="255"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Nights with no nighttime awakenings (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.4" spread="1.84"/>
                    <measurement group_id="O2" value="18.0" spread="1.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Days with no daytime symptoms (n=221, 220)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" spread="1.38"/>
                    <measurement group_id="O2" value="5.1" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Days able to perform daily activities(n=221,220)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.4" spread="2.09"/>
                    <measurement group_id="O2" value="8.5" spread="2.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Daily Number of Puffs of Rescue Medication</title>
        <description>The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect</description>
        <time_frame>52 weeks</time_frame>
        <population>Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Daily Number of Puffs of Rescue Medication</title>
          <description>The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect</description>
          <population>Only participants from the full analysis set, who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed.</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="251"/>
                <count group_id="O2" value="255"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Daily (n=231, 227)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.16" spread="0.199"/>
                    <measurement group_id="O2" value="-1.79" spread="0.199"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Daytime (n=221, 220)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.71" spread="0.112"/>
                    <measurement group_id="O2" value="-1.05" spread="0.112"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nighttime (n=226, 222)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.52" spread="0.094"/>
                    <measurement group_id="O2" value="-0.73" spread="0.095"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to First COPD Exacerbation (Moderate or Severe).</title>
        <description>COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.</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. Patients were analyzed according to the treatment to which they were randomized</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>12.5 μg twice-daily</description>
          </group>
          <group group_id="O2">
            <title>QAB149</title>
            <description>75 μg once-daily</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First COPD Exacerbation (Moderate or Severe).</title>
          <description>COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.</description>
          <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 to which they were randomized</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="251"/>
                <count group_id="O2" value="255"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="NA" lower_limit="NA" upper_limit="NA">NA - Insufficient number of participants with events</measurement>
                    <measurement group_id="O2" value="NA" lower_limit="NA" upper_limit="NA">NA - Insufficient number of participants with events</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>NVA237</title>
          <description>12.5 μg twice-daily</description>
        </group>
        <group group_id="E2">
          <title>QAB149</title>
          <description>75 μg once-daily</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="33" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ANGINA PECTORIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ARTERIOSCLEROSIS CORONARY ARTERY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CARDIAC ARREST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CARDIAC FAILURE CONGESTIVE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY STENOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPERTENSIVE HEART DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>STRESS CARDIOMYOPATHY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SUPRAVENTRICULAR TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>VENTRICULAR FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DYSPHAGIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>GASTROINTESTINAL HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INCARCERATED UMBILICAL HERNIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>LARGE INTESTINE POLYP</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SMALL INTESTINAL OBSTRUCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SWOLLEN TONGUE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </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="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>CHOLECYSTITIS CHRONIC</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>ABSCESS LIMB</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ACUTE SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>APPENDICITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DIVERTICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INFECTIVE EXACERBATION OF CHRONIC OBSTRUCTIVE AIRWAYS DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>LOBAR PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SEPSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>FEMORAL NECK FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HIP FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>JOINT INJURY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>POST-TRAUMATIC PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RADIATION OESOPHAGITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RIB FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SPINAL COMPRESSION FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>LIVER FUNCTION TEST ABNORMAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>FLUID OVERLOAD</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPERAMMONAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPOMAGNESAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPONATRAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>JOINT SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>OSTEOARTHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>BLADDER CANCER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>GLIOBLASTOMA MULTIFORME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INVASIVE DUCTAL BREAST CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>LUNG NEOPLASM MALIGNANT</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>OESOPHAGEAL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>PROSTATE CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SMALL CELL LUNG CANCER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>CAROTID ARTERY STENOSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CEREBRAL THROMBOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CEREBROVASCULAR ACCIDENT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CONVULSION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DYSARTHRIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>GENERALISED TONIC-CLONIC SEIZURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>PARTIAL SEIZURES</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>TRANSIENT ISCHAEMIC ATTACK</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ALCOHOL ABUSE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ALCOHOLISM</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>BIPOLAR DISORDER</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DYSPHORIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MENTAL STATUS CHANGES</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>NEPHROLITHIASIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RENAL FAILURE ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CHRONIC OBSTRUCTIVE PULMONARY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CHRONIC RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPOXIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RESPIRATORY ARREST</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SLEEP APNOEA SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>SKIN REACTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>URTICARIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>AORTIC DISSECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ARTERIOSCLEROSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DEEP VEIN THROMBOSIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </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="165" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="170" subjects_at_risk="256"/>
              </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="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN UPPER</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DENTAL CARIES</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>GASTROOESOPHAGEAL REFLUX DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>TOOTHACHE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>NON-CARDIAC CHEST PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>SEASONAL ALLERGY</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DIVERTICULITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS VIRAL</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>LOWER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>ORAL CANDIDIASIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RHINITIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>TOOTH ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION BACTERIAL</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="12" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>ARTHROPOD BITE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>CONTUSION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MUSCLE STRAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>PROCEDURAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>BLOOD PRESSURE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>WEIGHT DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </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="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPERLIPIDAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </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="7" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MUSCLE SPASMS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>MUSCULOSKELETAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>OSTEOARTHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>TENOSYNOVITIS STENOSANS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SYNCOPE</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>TREMOR</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>ANXIETY</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DEPRESSION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>INSOMNIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>HAEMATURIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="256"/>
              </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="83" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="88" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="18" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>HYPOXIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>PRODUCTIVE COUGH</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RHINITIS ALLERGIC</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SINUS CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>SPUTUM INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </event>
              <event>
                <sub_title>WHEEZING</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="256"/>
              </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="0" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="256"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="251"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="256"/>
              </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/NCT01697696
org study id: CNVA237A2319
secondary id: 2012-002728-34
nct id: NCT01697696
lead sponsor: 
has dmc: No
The purpose of the study is to provide long term safety data of NVA237. This study will
      assess the safety and tolerability of a single dose strength of NVA237.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Reporting Safety and Tolerability in Terms of Adverse Event (AE) Reporting Rate
time frame: 52 weeks
description: Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal lab finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgments of the investigators represent significant hazards.
measure: Time to Treatment Discontinuation
time frame: 52 Weeks
description: Discontinuation rates are calculated using the Kaplan Meier method. The protocol allowed patients to discontinue outside the treatment window, hence we have a patient who discontinued at Day 388. Reasons for discontinuing treatment are Subject/guardian decision, Adverse event, Protocol deviation Lack of efficacy, Physician decision, Dosing error, Disease improvement under study, Pregnancy, Technical problems
measure: Change From Baseline in Mean Forced Expiratory Volume (Average of the Two FEV1 Measurements 45 and 15 Minutes Pre-dose) in One Second at Week 52
time frame: -45 min and -15 minutes baseline and at Week 52
description: Change from baseline in pre-dose trough FEV1 was analyzed using a repeated measures analysis of covariance model which contained treatment, baseline FEV1, visit, baseline smoking status, baseline ICS use, COPD severity and treatment by visit, visit by baseline FEV1 interactions. An unstructured variance-covariance error matrix was used .Pulmonary function assessments were performed using centralized spirometry according to international standards. Pre-dose trough FEV1 was defined as the mean of FEV1 at -45 min and -15 min before the morning dose at Week 52. Baseline FEV1 was defined as the mean of the pre-dose FEV1 at -45 min and -15 min on Day 1.
measure: Change From Baseline in Pre-dose Forced Expiratory Volume (FEV1) in One Second at All Post Baseline Timepoints
time frame: -45 min and -15 minutes baseline and at Week 52
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.
measure: Change From Baseline in Pre-dose Forced Vital Capacity (FVC) at All Post-baseline Timepoints
time frame: -45 min and -15 minutes baseline and at Week 52
description: Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1.
measure: Change From Baseline in COPD Symptoms
time frame: 52 weeks
description: The total symptom score was defined as the sum of individual cores for respiratory symptoms, cough, wheeze, amount of sputum, color of sputum, and reathlessness. Where a patient had a morning score and an evening score for an individual symptom on one particular day then the worst score was to be taken as the daily score for that symptom. Each symptom scale ranged from 0-3 where 0 was no symptoms and 3 was the worst. The total daily/daytime/nighttime symptom score consists of looking at the score for 6 symptoms and can therefore have a minimum score of 0 or a maximum of 18.
measure: Change From Baseline in COPD Symptoms
time frame: 52 weeks
description: Percentage of days with 'no daytime symptoms' A day with 'no daytime symptoms' was defined from the diary data as any day where the patient had recorded in the evening no cough, no wheeze, no production of sputum and no feeling of breathlessness (other than when running) and no puffs of rescue medication during the past 12 hours (approximately 8 am to 8pm). However, a patient was not considered symptom free if they had used rescue medication that day even if his/her total daytime symptoms score was zero. Percentage of nights with 'no nighttime awakenings' A night with 'no nighttime awakenings' was defined from diary data as any night where the patient did not wake up due to symptoms. The total number of nights with 'no nighttime awakenings' over the treatment period was divided by the total number of nights where diary recordings had been made in order to derive the percentage nights with 'no nighttime awakenings'.
measure: Change From Baseline in Mean Daily Number of Puffs of Rescue Medication
time frame: 52 weeks
description: The number of puffs of rescue medication taken in the previous 12 hours was recorded by the patients in the eDiary in the morning and evening. The total number of puffs of rescue medication per day over the 52 week treatment period was calculated and divided by the total number of days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient. If the number of puffs was missing for part of the day (either morning or evening), then a half day was used in the denominator. Change from baseline in number of puffs were analyzed using a linear mixed model which contained treatment, baseline number of puffs, baseline smoking status, baseline ICS use and COPD disease severity as fixed effects with center as a random effect
measure: Time to First COPD Exacerbation (Moderate or Severe).
time frame: 52 weeks
description: COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if hospitalizations were required. Rates are calculated using the Kaplan Meier method.
arm group label: NVA237 dose 1
arm group type: Experimental
description: NVA237 dose 1
arm group label: Long-acting beta 2-agonist (LABA)
arm group type: Active Comparator
description: QAB149
intervention type: Drug
intervention name: NVA237
description: NVA237 will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI
arm group label: NVA237 dose 1
intervention type: Drug
intervention name: Long-acting beta 2-agonist (LABA)
description: QAB149 and matching placebo will be supplied in capsule form in blister packs for use in the Novartis Concept 1 SDDPI
arm group label: Long-acting beta 2-agonist (LABA)
intervention type: Drug
intervention name: Placebo
description: Placebo to match QAB149
arm group label: Long-acting beta 2-agonist (LABA)
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
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country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
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