<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/NCT01709864</url>
  </required_header>
  <id_info>
    <org_study_id>CNVA237A2317</org_study_id>
    <nct_id>NCT01709864</nct_id>
  </id_info>
  <brief_title>NVA237 Versus Placebo 12-week Efficacy Study</brief_title>
  <official_title>A 12-week Multi-center, Randomized, Double-blind, Placebo Controlled Study to Assess the Efficacy and Safety of NVA237 in Stable COPD Patients</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 study serves to determine whether the treatment of patients with stable, symptomatic&#xD;
      Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is&#xD;
      efficient and safe. The efficacy and safety of the drug will be tested against a placebo&#xD;
      treatment.&#xD;
&#xD;
      The primary criterion to assess efficacy will be the difference between the serial lung&#xD;
      function measurements of patients who have been treated for 12 weeks with NVA237 versus those&#xD;
      that have received placebo treatment for 12 weeks. A serial lung function measurement (FEV1&#xD;
      testing) will be conducted and the &quot;area under the curve&quot; will be the measure for the ability&#xD;
      to breathe.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing</measure>
    <time_frame>12 weeks</time_frame>
    <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit</measure>
    <time_frame>Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)</time_frame>
    <description>Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)</measure>
    <time_frame>Day 1 and Week 12 (Day 85)</time_frame>
    <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire</measure>
    <time_frame>Week 12</time_frame>
    <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Clinically Important Improvement of &gt;=4units in the SGRQ Total Score at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Daily Symptom Scores</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am &amp; pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Morning and Nighttime Symptom Scores at Week 12</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am &amp; each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Nights With &quot;no Nighttime Awakenings&quot;</measure>
    <time_frame>from Baseline up to 12 weeks</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. A night with &quot;no nighttime awakening&quot; is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days With &quot;no Daytime Symptoms&quot;</measure>
    <time_frame>from Baseline up to 12 weeks</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. A day with &quot;no daytime symptoms&quot; is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</measure>
    <time_frame>from Baseline up to 12 weeks</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. A &quot;day able to perform usual daily activities&quot; is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Average Number of Puffs of Rescue Medication Per Day</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Days Without Rescue Medication Use</measure>
    <time_frame>12 weeks</time_frame>
    <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</measure>
    <time_frame>Baseline, Day 1 and Week 12 (Day 85)</time_frame>
    <description>The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</measure>
    <time_frame>Baseline, Day 1 and Week 12 (Day 85)</time_frame>
    <description>The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">440</enrollment>
  <condition>Chronic Obstructive Pulmonary Disease</condition>
  <arm_group>
    <arm_group_label>NVA237</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NVA237</intervention_name>
    <description>NVA237 (glycopyrronium bromide) as a powder for inhalation in single-dose capsules.</description>
    <arm_group_label>NVA237</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo powder for inhalation in single-dose capsules (matching those for NVA237).</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Patients with stable, symptomatic Chronic Obstructive Pulmonary Disease (COPD) with&#xD;
             airflow obstruction of level 2 and 3 according to the current Global initiative for&#xD;
             chronic Obstructive Lung Disease (GOLD) strategy (2011).&#xD;
&#xD;
          2. Patients with Forced Expiratory Volume in one second (FEV1) ≥ 30% and &lt;80 % of the&#xD;
             predicted normal, and FEV1/ Forced Vital Capacity (FVC) &lt; 0.70 when measured 45 min&#xD;
             after the inhalation of 84 µg ipratropium bromide.&#xD;
&#xD;
          3. Current or ex-smokers with at least 10 cigarette pack years smoking history.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients with a history of long QT syndrome, with a prolonged QTc measured during&#xD;
             screening, or patients who have a clinically significant ECG abnormality at screening.&#xD;
&#xD;
          2. History of malignancy of any organ system (other than localized basal cell carcinoma&#xD;
             of the skin), treated or untreated, within the past 5 years, regardless of whether&#xD;
             there is evidence of local recurrence or metastases.&#xD;
&#xD;
          3. Pregnant or nursing (lactating) women. Women of childbearing potential unless using an&#xD;
             effective method of contraception.&#xD;
&#xD;
          4. Patients who in the judgment of the investigator, would be at potential risk if&#xD;
             enrolled into the study.&#xD;
&#xD;
          5. Patients who have a clinically significant concomitant disease at screening, including&#xD;
             but not limited to clinically significant laboratory abnormalities, clinically&#xD;
             significant renal, cardiovascular, neurological, endocrine, immunological,&#xD;
             psychiatric, gastrointestinal, hepatic, or hematological abnormalities, or with&#xD;
             uncontrolled diabetes, which could interfere with the assessment of the efficacy and&#xD;
             safety of the study treatment.&#xD;
&#xD;
          6. Patients with a body mass index (BMI) of more than 40 kg/m2.&#xD;
&#xD;
          7. Patients contraindicated for treatment with, or having a history of reactions/&#xD;
             hypersensitivity to anticholinergic agents, long and short acting beta-2 agonists, or&#xD;
             sympathomimetic amines.&#xD;
&#xD;
          8. Patients with any history of asthma, with onset of symptoms prior to age 40 years, or&#xD;
             patients with a high blood eosinophil count during screening.&#xD;
&#xD;
        Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Homewood</city>
        <state>Alabama</state>
        <zip>35209-6870</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Jasper</city>
        <state>Alabama</state>
        <zip>35501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>*See Various Dept.'s*</city>
        <state>Arizona</state>
        <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>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</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>San Diego</city>
        <state>California</state>
        <zip>92117-4946</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92120</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brandon</city>
        <state>Florida</state>
        <zip>33511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Defuniak Springs</city>
        <state>Florida</state>
        <zip>32435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Edgewater</city>
        <state>Florida</state>
        <zip>32132</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33156</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33173</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33186</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>Pompano Beach</city>
        <state>Florida</state>
        <zip>33060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Port Orange</city>
        <state>Florida</state>
        <zip>32127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sarasota</city>
        <state>Florida</state>
        <zip>34233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>South Miami</city>
        <state>Florida</state>
        <zip>33143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Summerfield</city>
        <state>Florida</state>
        <zip>34491</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tamarac</city>
        <state>Florida</state>
        <zip>33321</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Winter Park</city>
        <state>Florida</state>
        <zip>32789</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Shelby</city>
        <state>North Carolina</state>
        <zip>28152</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406-7108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Ninety Six</city>
        <state>South Carolina</state>
        <zip>29666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rock Hll</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29678</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Simpsonville</city>
        <state>South Carolina</state>
        <zip>29681</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Union</city>
        <state>South Carolina</state>
        <zip>29379</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Amarillo</city>
        <state>Texas</state>
        <zip>79106-4165</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <zip>76012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <zip>76014</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Beaumont</city>
        <state>Texas</state>
        <zip>77701</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75251</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Huntsville</city>
        <state>Texas</state>
        <zip>77340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Waco</city>
        <state>Texas</state>
        <zip>76712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2015</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>October 12, 2014</results_first_submitted>
  <results_first_submitted_qc>February 11, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 12, 2015</results_first_posted>
  <last_update_submitted>February 12, 2015</last_update_submitted>
  <last_update_submitted_qc>February 12, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 4, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Anticholinergic</keyword>
  <keyword>Antimuscarinic</keyword>
  <keyword>Chronic Obstructive Airway Disease</keyword>
  <keyword>Chronic Obstructive Lung Disease</keyword>
  <keyword>Chronic Obstructive Pulmonary Disease</keyword>
  <keyword>COPD</keyword>
  <keyword>LAMA</keyword>
  <keyword>Lung Disease</keyword>
  <keyword>Lung Diseases, Obstructive</keyword>
  <keyword>Lung Function</keyword>
  <keyword>Muscarinic receptor antagonist</keyword>
  <keyword>Pulmonary Disease, Chronic Obstructive</keyword>
  <keyword>Respiratory Tract Diseases</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>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="222"/>
                <participants group_id="P2" count="219"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="222">FAS included all randomized patients who received at least one dose of trial drug.</participants>
                <participants group_id="P2" count="216">FAS included all randomized patients who received at least one dose of trial drug.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Per Protocol Set (PPS)</title>
              <participants_list>
                <participants group_id="P1" count="204">PPS included all patients in the FAS who did not have any major protocol deviations.</participants>
                <participants group_id="P2" count="201">PPS included all patients in the FAS who did not have any major protocol deviations.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="215"/>
                <participants group_id="P2" count="208"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>subject/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>non-compliance with study treatment</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>NVA237</title>
          <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</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="222"/>
            <count group_id="B2" value="219"/>
            <count group_id="B3" value="441"/>
          </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="62.7" spread="8.36"/>
                    <measurement group_id="B2" value="62.1" spread="8.34"/>
                    <measurement group_id="B3" value="62.4" spread="8.34"/>
                  </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="98"/>
                    <measurement group_id="B2" value="87"/>
                    <measurement group_id="B3" value="185"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="124"/>
                    <measurement group_id="B2" value="132"/>
                    <measurement group_id="B3" value="256"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing</title>
        <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.</description>
        <time_frame>12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing</title>
          <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12</population>
          <units>liters*hr</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.125" spread="0.0162"/>
                    <measurement group_id="O2" value="-0.014" spread="0.0165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit</title>
        <description>Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose</description>
        <time_frame>Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit</title>
          <description>Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Trough FEV1 Day 2 (n=218, n=214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.141" spread="0.0124"/>
                    <measurement group_id="O2" value="0.025" spread="0.0122"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Trough FEV1 Day 86 (n=218, n=214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.0171"/>
                    <measurement group_id="O2" value="0.007" spread="0.0173"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-dose Trough FEV1 Day 15 (n=217, n=208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.112" spread="0.0135"/>
                    <measurement group_id="O2" value="-0.002" spread="0.0135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-dose Trough FEV1 Day 29 (n=217, n=208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0105" spread="0.0137"/>
                    <measurement group_id="O2" value="-0.005" spread="0.0136"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-dose Trough FEV1 Day 57 (n=217, n=208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0106" spread="0.0156"/>
                    <measurement group_id="O2" value="-0.006" spread="0.0157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-dose Trough FEV1 Day 85 (n=217, n=208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.090" spread="0.0155"/>
                    <measurement group_id="O2" value="-0.029" spread="0.0157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)</title>
        <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.</description>
        <time_frame>Day 1 and Week 12 (Day 85)</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)</title>
          <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Day 1and Week 12</population>
          <units>liters*hr</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FEV1, AUC 0-12h Day 1 (n=222, n=216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.140" spread="0.0108"/>
                    <measurement group_id="O2" value="-0.001" spread="0.0106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 0-4h Day 1 (n=222, n=216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.174" spread="0.0103"/>
                    <measurement group_id="O2" value="0.021" spread="0.0101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 0-4h Day 85 (n=222, n=216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.171" spread="0.0163"/>
                    <measurement group_id="O2" value="0.001" spread="0.0167"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 4-8h Day 1 (n=222, n=215)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.138" spread="0.0123"/>
                    <measurement group_id="O2" value="0.001" spread="0.0121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 4-8h Day 85 (n=222, n=215)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.115" spread="0.0172"/>
                    <measurement group_id="O2" value="-0.017" spread="0.0174"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 8-12h Day 1 (n=222, n=215)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.102" spread="0.0122"/>
                    <measurement group_id="O2" value="-0.037" spread="0.0120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, AUC 8-12h Day 85 (n=222, n=215)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.074" spread="0.0166"/>
                    <measurement group_id="O2" value="-0.034" spread="0.0168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire</title>
        <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).</description>
        <time_frame>Week 12</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire</title>
          <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</population>
          <units>score</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="210"/>
                <count group_id="O2" value="192"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.4" spread="0.96"/>
                    <measurement group_id="O2" value="-1.7" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Clinically Important Improvement of &gt;=4units in the SGRQ Total Score at Week 12</title>
        <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.</description>
        <time_frame>Week 12</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Clinically Important Improvement of &gt;=4units in the SGRQ Total Score at Week 12</title>
          <description>The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</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="210"/>
                <count group_id="O2" value="192"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.0"/>
                    <measurement group_id="O2" value="40.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12</title>
        <description>Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.</description>
        <time_frame>Week 12</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12</title>
          <description>Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</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="200"/>
                <count group_id="O2" value="188"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.46" spread="0.289"/>
                    <measurement group_id="O2" value="0.54" spread="0.286"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Daily Symptom Scores</title>
        <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am &amp; pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
        <time_frame>12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Daily Symptom Scores</title>
          <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am &amp; pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame.</population>
          <units>Score</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="211"/>
                <count group_id="O2" value="204"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.39" spread="0.139"/>
                    <measurement group_id="O2" value="-1.01" spread="0.135"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Morning and Nighttime Symptom Scores at Week 12</title>
        <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am &amp; each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
        <time_frame>12 weeks</time_frame>
        <population>Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only and included all randomized patients who received at least one dose of study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Morning and Nighttime Symptom Scores at Week 12</title>
          <description>Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am &amp; each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least &amp; 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day &amp; night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day &amp; night scores.</description>
          <population>Participants from the full analysis set (FAS), who had outcome measure data with applicable fixed effects/covariates according to the analysis model, were analyzed only and included all randomized patients who received at least one dose of study drug.</population>
          <units>score</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Daytime total symptom score (n=208,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.14" spread="0.133"/>
                    <measurement group_id="O2" value="-0.73" spread="0.130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>nighttime total symptom score (n=207,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.22" spread="0.143"/>
                    <measurement group_id="O2" value="-0.95" spread="0.139"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Nights With &quot;no Nighttime Awakenings&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. A night with &quot;no nighttime awakening&quot; is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.</description>
        <time_frame>from Baseline up to 12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Nights With &quot;no Nighttime Awakenings&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. A night with &quot;no nighttime awakening&quot; is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
          <units>percentage of 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="207"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.3" spread="2.00"/>
                    <measurement group_id="O2" value="11.3" spread="1.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days With &quot;no Daytime Symptoms&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. A day with &quot;no daytime symptoms&quot; is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.</description>
        <time_frame>from Baseline up to 12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days With &quot;no Daytime Symptoms&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. A day with &quot;no daytime symptoms&quot; is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
          <units>percentage of days</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="208"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1" spread="1.65"/>
                    <measurement group_id="O2" value="2.5" spread="1.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. A &quot;day able to perform usual daily activities&quot; is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.</description>
        <time_frame>from Baseline up to 12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. A &quot;day able to perform usual daily activities&quot; is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization</population>
          <units>pecentage of days</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="208"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" spread="2.20"/>
                    <measurement group_id="O2" value="1.8" spread="2.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Average Number of Puffs of Rescue Medication Per Day</title>
        <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>The Average Number of Puffs of Rescue Medication Per Day</title>
          <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. Week 12</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="211"/>
                <count group_id="O2" value="204"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.63" spread="0.180"/>
                    <measurement group_id="O2" value="-0.86" spread="0.177"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Days Without Rescue Medication Use</title>
        <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.</description>
        <time_frame>12 weeks</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Days Without Rescue Medication Use</title>
          <description>Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug, patients were analyzed according to the treatment they were assigned to at randomization. However, for a given time frame, analyzed participants had values at both baseline and the corresponding time frame, i.e. week 12</population>
          <units>percentage of days</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="209"/>
                <count group_id="O2" value="202"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.6" spread="2.37"/>
                    <measurement group_id="O2" value="10.5" spread="2.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</title>
        <description>The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
        <time_frame>Baseline, Day 1 and Week 12 (Day 85)</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</title>
          <description>The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DAY 1/ 5 min (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.175" spread="0.0152"/>
                    <measurement group_id="O2" value="0.037" spread="0.0152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 15 min (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.265" spread="0.0181"/>
                    <measurement group_id="O2" value="0.044" spread="0.0180"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 1h (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.318" spread="0.0207"/>
                    <measurement group_id="O2" value="0.032" spread="0.0205"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 2h (n=221, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.351" spread="0.0216"/>
                    <measurement group_id="O2" value="0.071" spread="0.0213"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 4h (n=220, 213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.290" spread="0.0235"/>
                    <measurement group_id="O2" value="0.067" spread="0.0231"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 6h (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.252" spread="0.0235"/>
                    <measurement group_id="O2" value="0.022" spread="0.0234"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 8h (n=220, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.192" spread="0.0221"/>
                    <measurement group_id="O2" value="-0.009" spread="0.0220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 11h 55min (n=216, 207)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.152" spread="0.0234"/>
                    <measurement group_id="O2" value="-0.030" spread="0.0235"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ -45 min (n=217, 208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.162" spread="0.0289"/>
                    <measurement group_id="O2" value="-0.043" spread="0.0296"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ -15 min (n=216, 208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.156" spread="0.0283"/>
                    <measurement group_id="O2" value="-0.017" spread="0.0287"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 5 min (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.184" spread="0.0282"/>
                    <measurement group_id="O2" value="-0.007" spread="0.0287"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 15 min (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.263" spread="0.0288"/>
                    <measurement group_id="O2" value="-0.003" spread="0.0294"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 1h (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.258" spread="0.0297"/>
                    <measurement group_id="O2" value="0.004" spread="0.0302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 2h (n=221, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.277" spread="0.0299"/>
                    <measurement group_id="O2" value="0.033" spread="0.0307"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 4h (n=220, 213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.215" spread="0.0317"/>
                    <measurement group_id="O2" value="0.076" spread="0.0321"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 6h (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.199" spread="0.0304"/>
                    <measurement group_id="O2" value="-0.015" spread="0.0305"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 8h (n=220, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.128" spread="0.0303"/>
                    <measurement group_id="O2" value="-0.023" spread="0.0305"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 11h 55min (n=216, 207)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.110" spread="0.0286"/>
                    <measurement group_id="O2" value="-0.006" spread="0.0288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</title>
        <description>The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
        <time_frame>Baseline, Day 1 and Week 12 (Day 85)</time_frame>
        <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.</population>
        <group_list>
          <group group_id="O1">
            <title>NVA237</title>
            <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)</title>
          <description>The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.</description>
          <population>The full analysis set (FAS): all randomized patients who received at least one dose of trial drug. Following the intent-to -treat principle, patients were analyzed according to the treatment they were assigned to at randomization.</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="222"/>
                <count group_id="O2" value="216"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>DAY 1/ 5 min (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.074" spread="0.0075"/>
                    <measurement group_id="O2" value="0.015" spread="0.0074"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 15 min (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.129" spread="0.0085"/>
                    <measurement group_id="O2" value="0.015" spread="0.0084"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 1h (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.176" spread="0.0108"/>
                    <measurement group_id="O2" value="0.008" spread="0.0106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 2h (n=221, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.198" spread="0.0120"/>
                    <measurement group_id="O2" value="0.031" spread="0.0118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 4h (n=220, 213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.168" spread="0.0132"/>
                    <measurement group_id="O2" value="0.028" spread="0.0129"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 6h (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.132" spread="0.0135"/>
                    <measurement group_id="O2" value="0.000" spread="0.0134"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 8h (n=220, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.113" spread="0.0129"/>
                    <measurement group_id="O2" value="-0.022" spread="0.0128"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 1/ 11h 55min (n=216, 207)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.083" spread="0.0131"/>
                    <measurement group_id="O2" value="-0.046" spread="0.0131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ -45 min (n=217, 208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.092" spread="0.0154"/>
                    <measurement group_id="O2" value="-0.040" spread="0.0158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ -15 min (n=216, 208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.090" spread="0.0160"/>
                    <measurement group_id="O2" value="-0.022" spread="0.0162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 5 min (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.118" spread="0.0161"/>
                    <measurement group_id="O2" value="-0.018" spread="0.0163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 15 min (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.171" spread="0.0164"/>
                    <measurement group_id="O2" value="-0.016" spread="0.0168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 1h (n=222, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.178" spread="0.0166"/>
                    <measurement group_id="O2" value="-0.014" spread="0.0169"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 2h (n=221, 216)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.186" spread="0.0178"/>
                    <measurement group_id="O2" value="0.006" spread="0.0183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 4h (n=220, 213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.147" spread="0.0180"/>
                    <measurement group_id="O2" value="0.014" spread="0.0182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 6h (n=221, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.120" spread="0.0183"/>
                    <measurement group_id="O2" value="-0.026" spread="0.0183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 8h (n=220, 214)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.080" spread="0.0180"/>
                    <measurement group_id="O2" value="-0.036" spread="0.0181"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DAY 85/ 11h 55min (n=216, 207)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.072" spread="0.0165"/>
                    <measurement group_id="O2" value="-0.043" spread="0.0165"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>NVA237</title>
          <description>NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.</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="11" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE CORONARY SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>ACUTE MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>ANGINA PECTORIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>ATRIAL FIBRILLATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>CARDIAC ARREST</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>CARDIAC FAILURE CONGESTIVE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>CORONARY ARTERY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>VENTRICULAR TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>PANCREATITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </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="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>SYSTEMIC INFLAMMATORY RESPONSE SYNDROME</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION BACTERIAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>WOUND INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>GUN SHOT WOUND</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>HEAT STROKE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>LUMBAR VERTEBRAL FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>VOLUME BLOOD DECREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>LUNG NEOPLASM MALIGNANT</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>SUBARACHNOID HAEMORRHAGE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>RENAL FAILURE ACUTE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </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="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>CHRONIC OBSTRUCTIVE PULMONARY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0.9</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="72" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="66" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>VERTIGO</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>VISION BLURRED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>ABDOMINAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>BRONCHITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS VIRAL</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>INFLUENZA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>LOWER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>ORAL CANDIDIASIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>TOOTH ABSCESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION BACTERIAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>EXCORIATION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>HYPOKALAEMIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHROPATHY</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="216"/>
              </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="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>CHRONIC OBSTRUCTIVE PULMONARY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="216"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="216"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="222"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="216"/>
              </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/NCT01709864
org study id: CNVA237A2317
nct id: NCT01709864
lead sponsor: 
has dmc: No
The study serves to determine whether the treatment of patients with stable, symptomatic
      Chronic Obstructive Pulmonary Disease (COPD) with the investigational drug NVA237 is
      efficient and safe. The efficacy and safety of the drug will be tested against a placebo
      treatment.

      The primary criterion to assess efficacy will be the difference between the serial lung
      function measurements of patients who have been treated for 12 weeks with NVA237 versus those
      that have received placebo treatment for 12 weeks. A serial lung function measurement (FEV1
      testing) will be conducted and the "area under the curve" will be the measure for the ability
      to breathe.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline of Standardized Area Under the Curve (AUC) for Forced Expiratory Volume in One Second (FEV1) Post Dosing
time frame: 12 weeks
description: The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) at week 12 of treatment. Serial lung function measurements are taken at various time points following dosing at week 12 to calculate the AUC.
measure: Change From Baseline in Trough FEV1 and Pre-dose Trough FEV1 by Visit
time frame: Day 2, 86 (trough) Day 15, 29, 57, 85 (pre-dose trough)
description: Trough Forced Expiratory Volume in one second (FEV1) is the mean of FEV1 at 23h 15min and 23h 45min after the morning dose of the previous day. Pre-dose trough FEV1 is the mean of FEV1 at -45min and -15min before morning dose
measure: Change From Baseline in FEV1 AUC (0-12H) at Day 1 and FEV1 AUC (0-4h), AUC (4-8h), AUC (8-12h) at Day 1 and Week 12 (Day 85)
time frame: Day 1 and Week 12 (Day 85)
description: The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) is assessed for different time spans within the overall serial measurement post dosing (FEV1 AUCs Time Spans), at day 1 and at week 12 of treatment. Serial lung function measurements are taken at various time points post dosing on day 1 and at week 12 to calculate the AUC for these different time spans.
measure: Change From Baseline in the Health Status Assessed by St. George's Respiratory Questionnaire
time frame: Week 12
description: The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The SGRQ is a 50 item scale assessing symptoms, patient activities and impact of the disease. Scores range from 0 to 100 units, with higher scores indicating more limitations. The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically meaningful improvement (MCID) in SGRQ is defined as a decrease of 4 or more units of the SGRQ scale in the total score, as compared to baseline (change from baseline).
measure: Percentage of Participants With a Clinically Important Improvement of >=4units in the SGRQ Total Score at Week 12
time frame: Week 12
description: The health status, as reported by the patients, is assessed using the St. George's Respiratory Questionnaire (SGRQ). The assessment is based on total score as well as the percentage of patients with clinically significant improvement at week 12 versus day 1. A clinically significant improvement in SGRQ is defined as less than or equal to -4 change from baseline.
measure: Breathlessness Assessed by Transition Dyspnea Index (TDI) Focal Score at Week 12
time frame: Week 12
description: Breathlessness at week 12 is measured using the Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the Baseline Dyspnea Index (BDI). Patients are considered to have clinically significant improvement with the TDI score change versus BDI being equal to or greater than 1. TDI focal score is based on three domains: functional impairment, magnitude of task and magnitude of effort. Each domain is scored from -3 (major deterioration) to 3 (major improvement) to give an overall TDI focal score of -9 to 9. Higher numbers indicate a better score.
measure: Change From Baseline of Daily Symptom Scores
time frame: 12 weeks
description: Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am and each pm. Each question can be answered w/1 of 4 pre-defined answers, with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of combined daily symptom scores(combined from am & pm)for each patient over 12 weeks. The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. Patients may have met the min. response requirements for the night scores(am questions),but not for the day scores(pm questions)or vice versa, the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores.
measure: Change From Baseline of Morning and Nighttime Symptom Scores at Week 12
time frame: 12 weeks
description: Patients reported symptoms using an electronic diary.The diary has 9 symptom questions each am & each pm.Each question can be answered w/1 of 4 pre-defined answers,with a unit value of 0-3, 0 is least & 3 is most severe symptom.Symptom scores are calculated as the mean of the symptom scores(either the score assessed in am for the previous 12 hrs-referred to as nighttime scores,or the score assessed in pm for the previous 12 hrs-referred to as the daytime symptom score) for each patient over 12 weeks.The baseline is calculated from the run-in epoch prior to randomization.The change from baseline is in LS mean daily symptom scores over the 12 weeks. If the mean score over the 12 weeks is lower than the baseline, result is (-).A neg. result indicates an improvement in COPD symptom severity. the # of patients analyzed can vary between both day & night scores. Therefore, the # of patients analyzed for the combined daily symptom score can vary from the #s for individual day & night scores.
measure: Percentage of Nights With "no Nighttime Awakenings"
time frame: from Baseline up to 12 weeks
description: Patients are reporting symptoms by using an electronic diary. A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. Percentage of no nighttime awakenings from Baseline up to 12 weeks.
measure: Percentage of Days With "no Daytime Symptoms"
time frame: from Baseline up to 12 weeks
description: Patients are reporting symptoms by using an electronic diary. A day with "no daytime symptoms" is defined from diary data as any day where the patient has recorded in the evening no cough, no wheeze, no production of sputum, and no feeling of breathlessness (other than when running) during the past approximately 12 hours. The percentage of days is calculated by the number of days with no daytime symptoms/total number of days with evaluable data X 100.
measure: Percentage of "Days Able to Perform Usual Daily Activities"
time frame: from Baseline up to 12 weeks
description: Patients are reporting symptoms by using an electronic diary. A "day able to perform usual daily activities" is defined from diary data as any day where the patient was not prevented from performing their usual daily activities due to respiratory symptoms.
measure: The Average Number of Puffs of Rescue Medication Per Day
time frame: baseline and 12 weeks
description: Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the mean daily number of puffs used per patient over the 12 weeks treatment period.
measure: Percentage of Days Without Rescue Medication Use
time frame: 12 weeks
description: Patients report the number of puffs of rescue medication (salbutamol / albuterol) using an electronic diary. The use of rescue medication is analyzed as the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization.
measure: Change From Baseline of Forced Vital Capacity (FVC) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
time frame: Baseline, Day 1 and Week 12 (Day 85)
description: The Forced Vital Capacity (FVC) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
measure: Change From Baseline of Forced Expiratory Volume in One Second (FEV1) at All Individual Timepoints at Day 1 and at Week 12 (Day 85)
time frame: Baseline, Day 1 and Week 12 (Day 85)
description: The Forced Expiratory Volume in one second (FEV1) assessments for all individual time points of the serial measurements on day 1 and at week 12 are analyzed.
arm group label: NVA237
arm group type: Experimental
description: NVA237 will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo will be inhaled from a single-dose dry powder inhaler for a period of 12 weeks.
intervention type: Drug
intervention name: NVA237
description: NVA237 (glycopyrronium bromide) as a powder for inhalation in single-dose capsules.
arm group label: NVA237
intervention type: Drug
intervention name: Placebo
description: Placebo powder for inhalation in single-dose capsules (matching those for NVA237).
arm group label: Placebo
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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