<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/NCT01715298</url>
  </required_header>
  <id_info>
    <org_study_id>CNVA237A2318</org_study_id>
    <nct_id>NCT01715298</nct_id>
  </id_info>
  <brief_title>NVA237 BID Versus Placebo Twelve-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. The primary criterion to assess efficacy will be the difference between the serial&#xD;
      lung function measurements of patients who have been treated for 12 weeks with NVA237 versus&#xD;
      those that have received placebo treatment for 12 weeks. A serial lung function measurement&#xD;
      (FEV1 testing) will be conducted and the &quot;area under the curve&quot; will be the measure for the&#xD;
      ability to breathe.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 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 in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing</measure>
    <time_frame>Week 12</time_frame>
    <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing</measure>
    <time_frame>Day 1</time_frame>
    <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
.The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing</measure>
    <time_frame>Day 1 and Week 12</time_frame>
    <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) 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 the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints</measure>
    <time_frame>Day 1 and week 12</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. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Trough Forced Expiratory Volume in One Second</measure>
    <time_frame>Day 1 and week 12</time_frame>
    <description>Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1</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>Breathlessness Assessed by Transition Dyspnea Index</measure>
    <time_frame>Week 12</time_frame>
    <description>Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day</measure>
    <time_frame>Baseline and week 12</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 change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Percentage of Days Without Rescue Medication Use</measure>
    <time_frame>Baseline and week 12</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 change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Daily Symptom Scores</measure>
    <time_frame>day 1 to week 12</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Percentage of Nights With &quot;no Nighttime Awakenings&quot;</measure>
    <time_frame>Day 1 and week 12</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is &quot;no waking due to symptoms.&quot; 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. The change from baseline in the percentage of nights with &quot;no nighttime awakening&quot; is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Percentage of Days With &quot;no Daytime Symptoms&quot;</measure>
    <time_frame>Day 1 to week 12</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. 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 in the evening questionnaire. The change from baseline in the percentage of days with &quot;no daytime symptoms&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</measure>
    <time_frame>Day 1 to week 12</time_frame>
    <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (&quot;Did your respiratory symptoms stop you performing your usual daily activities today&quot;). The answer with the lowest symptom score is &quot;not at all.&quot; 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. The change from baseline in the percentage of &quot;days able to perform usual daily activities&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Forced Vital Capacity at All Individual Timepoints</measure>
    <time_frame>Day 1 and week 12</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. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Trough Forced Vital Capacity</measure>
    <time_frame>Day 1 and week 12</time_frame>
    <description>Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Morning and Nighttime Symptom Scores</measure>
    <time_frame>Day 1 to week 12</time_frame>
    <description>Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">432</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 (Glycopyrronioum 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: 1. Patients with stable, symptomatic Chronic Obstructive Pulmonary&#xD;
        Disease (COPD) with airflow obstruction of level 2 and 3 according to the current Global&#xD;
        initiative for chronic Obstructive Lung Disease (GOLD) strategy (2011). 2. Patients with&#xD;
        Forced Expiratory Volume in one second (FEV1) ≥ 30% and &lt;80 % of the predicted normal, and&#xD;
        FEV1/FVC &lt; 0.70 when measured 45 min 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-defnied 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>*See Various Dept.'s*</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93726</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>Yorba Linda</city>
        <state>California</state>
        <zip>92886-7921</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Yorba Linda</city>
        <state>California</state>
        <zip>92886</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <zip>80304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Wheat Ridge</city>
        <state>Colorado</state>
        <zip>80033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lynn Haven</city>
        <state>Florida</state>
        <zip>32444</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>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>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>Conyers</city>
        <state>Georgia</state>
        <zip>30094</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>River Forest</city>
        <state>Illinois</state>
        <zip>60305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Evansville</city>
        <state>Indiana</state>
        <zip>47714</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40509</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Sunset</city>
        <state>Louisiana</state>
        <zip>70584</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fall River</city>
        <state>Massachusetts</state>
        <zip>02720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>North Dartmouth</city>
        <state>Massachusetts</state>
        <zip>02747</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Plymouth</city>
        <state>Minnesota</state>
        <zip>55441</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Charles</city>
        <state>Missouri</state>
        <zip>63301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fremont</city>
        <state>Nebraska</state>
        <zip>68025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11234</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Great Neck</city>
        <state>New York</state>
        <zip>11021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Massapequa</city>
        <state>New York</state>
        <zip>11758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New Windsor</city>
        <state>New York</state>
        <zip>12553</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10003</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10028</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>Cincinnati</city>
        <state>Ohio</state>
        <zip>45231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45245</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504-8741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Langhorne</city>
        <state>Pennsylvania</state>
        <zip>19047</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15243</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Pottstown</city>
        <state>Pennsylvania</state>
        <zip>19464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tipton</city>
        <state>Pennsylvania</state>
        <zip>16684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>East Providence</city>
        <state>Rhode Island</state>
        <zip>02914</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Fort Mill</city>
        <state>South Carolina</state>
        <zip>29707</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>Denton</city>
        <state>Texas</state>
        <zip>76210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Midvale</city>
        <state>Utah</state>
        <zip>84047</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>South Burlington</city>
        <state>Vermont</state>
        <zip>05403</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2015</verification_date>
  <study_first_submitted>October 24, 2012</study_first_submitted>
  <study_first_submitted_qc>October 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 26, 2012</study_first_posted>
  <results_first_submitted>December 17, 2014</results_first_submitted>
  <results_first_submitted_qc>March 9, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 11, 2015</results_first_posted>
  <last_update_submitted>March 9, 2015</last_update_submitted>
  <last_update_submitted_qc>March 9, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">March 11, 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="216"/>
                <participants group_id="P2" count="216"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="215">patients were analyzed according to the treatment to which they were randomized</participants>
                <participants group_id="P2" count="214"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="209"/>
                <participants group_id="P2" count="205"/>
              </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>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Patient/guardian decision</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="9"/>
              </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="216"/>
            <count group_id="B2" value="216"/>
            <count group_id="B3" value="432"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.9" spread="8.55"/>
                    <measurement group_id="B2" value="64.2" spread="8.41"/>
                    <measurement group_id="B3" value="64.1" spread="8.47"/>
                  </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="88"/>
                    <measurement group_id="B2" value="90"/>
                    <measurement group_id="B3" value="178"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="128"/>
                    <measurement group_id="B2" value="126"/>
                    <measurement group_id="B3" value="254"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing</title>
        <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur</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. 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 Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing</title>
          <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur</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</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="215"/>
                <count group_id="O2" value="213"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.115" spread="0.0153"/>
                    <measurement group_id="O2" value="-0.008" spread="0.0153"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing</title>
        <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
.The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</description>
        <time_frame>Day 1</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 1</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 Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing</title>
          <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
.The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</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 1</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="215"/>
                <count group_id="O2" value="213"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.121" spread="0.0096"/>
                    <measurement group_id="O2" value="0.003" spread="0.0096"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing</title>
        <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) 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 the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</description>
        <time_frame>Day 1 and 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. 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 Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing</title>
          <description>The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) 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 the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.&#xD;
The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.</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</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="215"/>
                <count group_id="O2" value="214"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 AUC 0-4h (n=215,213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.154" spread="0.0088"/>
                    <measurement group_id="O2" value="0.014" spread="0.0088"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 AUC 0-4h (n=215,213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.153" spread="0.0159"/>
                    <measurement group_id="O2" value="0.004" spread="0.0159"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 AUC 4-8h (n=213,209)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.118" spread="0.0107"/>
                    <measurement group_id="O2" value="0.011" spread="0.0109"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 AUC 4-8h (n=213,209)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.107" spread="0.0159"/>
                    <measurement group_id="O2" value="0.000" spread="0.0158"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 AUC 8-12h (n=212,210)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.085" spread="0.0120"/>
                    <measurement group_id="O2" value="-0.021" spread="0.0120"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12 AUC 8-12h (n=212,210)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.075" spread="0.0164"/>
                    <measurement group_id="O2" value="-0.033" spread="0.0164"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints</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. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.</description>
        <time_frame>Day 1 and 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. 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 Forced Expiratory Volume in One Second at All Individual Timepoints</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. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.</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>Percent</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="215"/>
                <count group_id="O2" value="214"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FEV1, day 1, 5 min (n=207,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="8.67"/>
                    <measurement group_id="O2" value="-0.3" spread="7.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 15 min (n=209,201)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.9" spread="10.05"/>
                    <measurement group_id="O2" value="0.3" spread="7.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 1 h (n=205,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.9" spread="11.98"/>
                    <measurement group_id="O2" value="1.2" spread="9.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 2 h (n=201,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="14.42"/>
                    <measurement group_id="O2" value="2.5" spread="9.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 4 h (n=199,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.7" spread="13.39"/>
                    <measurement group_id="O2" value="2.2" spread="12.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 6h (n=197,197)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.3" spread="13.82"/>
                    <measurement group_id="O2" value="2.2" spread="11.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 8 h (n=200,189)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9" spread="14.43"/>
                    <measurement group_id="O2" value="-0.5" spread="12.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 1, 11 h 55min (n=184,182)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.6" spread="13.44"/>
                    <measurement group_id="O2" value="-1.7" spread="14.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, -45min (n=184,188)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" spread="17.61"/>
                    <measurement group_id="O2" value="1.7" spread="17.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, -15min (n=180,185)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.6" spread="18.23"/>
                    <measurement group_id="O2" value="2.7" spread="17.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 5min (n=185,178)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.4" spread="18.78"/>
                    <measurement group_id="O2" value="1.8" spread="17.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 15min (n=186,189)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.9" spread="20.00"/>
                    <measurement group_id="O2" value="2.0" spread="17.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 1h (n=184,187)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.8" spread="20.49"/>
                    <measurement group_id="O2" value="1.6" spread="17.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 2h (n=178,187)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="20.83"/>
                    <measurement group_id="O2" value="2.4" spread="18.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 4h (n=179,183)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" spread="19.72"/>
                    <measurement group_id="O2" value="3.5" spread="20.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 6h (n=174,172)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.8" spread="18.78"/>
                    <measurement group_id="O2" value="2.5" spread="20.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 8h (n=178,174)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="18.18"/>
                    <measurement group_id="O2" value="0.2" spread="18.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FEV1, day 85, 11h 55min (n=171,171)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2" spread="19.39"/>
                    <measurement group_id="O2" value="-2.1" spread="20.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Trough Forced Expiratory Volume in One Second</title>
        <description>Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1</description>
        <time_frame>Day 1 and 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. 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>Mean Trough Forced Expiratory Volume in One Second</title>
          <description>Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1</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</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="213"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.128" spread="0.0129"/>
                    <measurement group_id="O2" value="0.021" spread="0.0130"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.0166"/>
                    <measurement group_id="O2" value="0.038" spread="0.0166"/>
                  </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="193"/>
                <count group_id="O2" value="194"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.4" spread="1.08"/>
                    <measurement group_id="O2" value="-1.2" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Breathlessness Assessed by Transition Dyspnea Index</title>
        <description>Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.</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</title>
          <description>Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.</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="190"/>
                <count group_id="O2" value="190"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.95" spread="0.280"/>
                    <measurement group_id="O2" value="0.48" spread="0.277"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean 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 change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.</description>
        <time_frame>Baseline and 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 Mean 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 change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.</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="208"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.33" spread="0.163"/>
                    <measurement group_id="O2" value="-0.80" spread="0.160"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the 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 change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.</description>
        <time_frame>Baseline and 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 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 change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the 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="206"/>
                <count group_id="O2" value="198"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" spread="1.95"/>
                    <measurement group_id="O2" value="7.0" spread="1.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Daily Symptom Scores</title>
        <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.</description>
        <time_frame>day 1 to 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>Change From Baseline in Daily Symptom Scores</title>
          <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.</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="208"/>
                <count group_id="O2" value="201"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.09" spread="0.103"/>
                    <measurement group_id="O2" value="-0.80" spread="0.104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Percentage of Nights With &quot;no Nighttime Awakenings&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is &quot;no waking due to symptoms.&quot; 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. The change from baseline in the percentage of nights with &quot;no nighttime awakening&quot; is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.</description>
        <time_frame>Day 1 and week 12</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 in the Percentage of Nights With &quot;no Nighttime Awakenings&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is &quot;no waking due to symptoms.&quot; 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. The change from baseline in the percentage of nights with &quot;no nighttime awakening&quot; is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being 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. 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="208"/>
                <count group_id="O2" value="200"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" spread="1.52"/>
                    <measurement group_id="O2" value="9.2" spread="1.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Percentage of Days With &quot;no Daytime Symptoms&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. 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 in the evening questionnaire. The change from baseline in the percentage of days with &quot;no daytime symptoms&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.</description>
        <time_frame>Day 1 to week 12</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 in the Percentage of Days With &quot;no Daytime Symptoms&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. 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 in the evening questionnaire. The change from baseline in the percentage of days with &quot;no daytime symptoms&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. 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. 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="207"/>
                <count group_id="O2" value="195"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="1.17"/>
                    <measurement group_id="O2" value="2.6" spread="1.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</title>
        <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (&quot;Did your respiratory symptoms stop you performing your usual daily activities today&quot;). The answer with the lowest symptom score is &quot;not at all.&quot; 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. The change from baseline in the percentage of &quot;days able to perform usual daily activities&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.</description>
        <time_frame>Day 1 to week 12</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 in Percentage of &quot;Days Able to Perform Usual Daily Activities&quot;</title>
          <description>Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities (&quot;Did your respiratory symptoms stop you performing your usual daily activities today&quot;). The answer with the lowest symptom score is &quot;not at all.&quot; 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. The change from baseline in the percentage of &quot;days able to perform usual daily activities&quot; is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe 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. 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="207"/>
                <count group_id="O2" value="195"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2" spread="1.61"/>
                    <measurement group_id="O2" value="0.9" spread="1.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Forced Vital Capacity at All Individual Timepoints</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. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.</description>
        <time_frame>Day 1 and week 12</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 in Forced Vital Capacity at All Individual Timepoints</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. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.</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="215"/>
                <count group_id="O2" value="214"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>FVC, day 1, 5 min (n=214,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.120" spread="0.0129"/>
                    <measurement group_id="O2" value="-0.014" spread="0.0131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 15 min (n=214,213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.233" spread="0.0155"/>
                    <measurement group_id="O2" value="0.005" spread="0.0157"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 1 h (n=215,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.304" spread="0.0175"/>
                    <measurement group_id="O2" value="0.041" spread="0.0176"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 2 h (n=211,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.322" spread="0.0193"/>
                    <measurement group_id="O2" value="0.060" spread="0.0191"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 4 h (n=209,208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.247" spread="0.0196"/>
                    <measurement group_id="O2" value="0.048" spread="0.0195"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 6 h (n=208,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.225" spread="0.0219"/>
                    <measurement group_id="O2" value="0.051" spread="0.0220"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 8 h (n=209,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.200" spread="0.0228"/>
                    <measurement group_id="O2" value="-0.002" spread="0.0232"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 1, 11 h 55min (n=203,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.147" spread="0.0242"/>
                    <measurement group_id="O2" value="-0.017" spread="0.0243"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, -45 min (n=207,204)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.0248"/>
                    <measurement group_id="O2" value="0.008" spread="0.0246"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, -15 min (n=208,204)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.146" spread="0.0241"/>
                    <measurement group_id="O2" value="0.010" spread="0.0239"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 5 min (n=214,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.177" spread="0.0247"/>
                    <measurement group_id="O2" value="0.001" spread="0.0251"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 15 min (n=214,213)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.219" spread="0.0261"/>
                    <measurement group_id="O2" value="-0.003" spread="0.0259"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 1 hr (n=215,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.267" spread="0.0261"/>
                    <measurement group_id="O2" value="0.010" spread="0.0260"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 2 hr (n=211,211)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.275" spread="0.0277"/>
                    <measurement group_id="O2" value="0.024" spread="0.0271"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 4 hr (n=209,208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.204" spread="0.0281"/>
                    <measurement group_id="O2" value="0.035" spread="0.0278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 6 hr (n=208,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.185" spread="0.0278"/>
                    <measurement group_id="O2" value="0.016" spread="0.0278"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 8 hr (n=209,205)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.152" spread="0.0264"/>
                    <measurement group_id="O2" value="-0.015" spread="0.0266"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 11 hr 55min (n=203,202)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.135" spread="0.0290"/>
                    <measurement group_id="O2" value="-0.045" spread="0.0288"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 23 hr 15min (n=210,204)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.207" spread="0.0289"/>
                    <measurement group_id="O2" value="0.066" spread="0.0284"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>FVC, day 85, 23 hr 45min (n=213,208)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.228" spread="0.0292"/>
                    <measurement group_id="O2" value="0.095" spread="0.0290"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Trough Forced Vital Capacity</title>
        <description>Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.</description>
        <time_frame>Day 1 and week 12</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 in Mean Trough Forced Vital Capacity</title>
          <description>Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.</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="213"/>
                <count group_id="O2" value="208"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.249" spread="0.0225"/>
                    <measurement group_id="O2" value="0.078" spread="0.0227"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.210" spread="0.0277"/>
                    <measurement group_id="O2" value="0.080" spread="0.0276"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Morning and Nighttime Symptom Scores</title>
        <description>Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.</description>
        <time_frame>Day 1 to week 12</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 in Morning and Nighttime Symptom Scores</title>
          <description>Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.</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>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="215"/>
                <count group_id="O2" value="214"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Daytime total symptom score (n=207,195)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.86" spread="0.097"/>
                    <measurement group_id="O2" value="-0.61" spread="0.100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nighttime total symptom score (n=208,200)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.03" spread="0.101"/>
                    <measurement group_id="O2" value="-0.76" spread="0.102"/>
                  </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="9" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>ACUTE MYOCARDIAL INFARCTION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>ANGINA PECTORIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>CELLULITIS</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>HERPES SIMPLEX</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>OPHTHALMIC HERPES ZOSTER</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>PNEUMONIA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>SPINAL COMPRESSION FRACTURE</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>METASTATIC SQUAMOUS CELL CARCINOMA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>SQUAMOUS CELL CARCINOMA OF THE VULVA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>CHRONIC OBSTRUCTIVE PULMONARY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>HAEMOPTYSIS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>PULMONARY MASS</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>RESPIRATORY FAILURE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>PERIPHERAL ARTERY ANEURYSM</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </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="88" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="81" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>VISION BLURRED</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>CONSTIPATION</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>DRY MOUTH</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>OEDEMA PERIPHERAL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </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="216"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>CANDIDA INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>CELLULITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>GASTROENTERITIS VIRAL</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>NASOPHARYNGITIS</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>ORAL CANDIDIASIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>SINUSITIS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>URINARY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>VIRAL UPPER RESPIRATORY TRACT INFECTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>ACCIDENTAL OVERDOSE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>FALL</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>MUSCLE STRAIN</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>PROCEDURAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>BLOOD PRESSURE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>ARTHRITIS</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>BACK PAIN</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>PAIN IN EXTREMITY</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>CHRONIC OBSTRUCTIVE PULMONARY DISEASE</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="43" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>COUGH</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>DYSPNOEA</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>NASAL CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>OROPHARYNGEAL PAIN</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>RESPIRATORY TRACT CONGESTION</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>RHINITIS ALLERGIC</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="214"/>
              </event>
              <event>
                <sub_title>RHINORRHOEA</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="214"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>RASH</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </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="216"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="214"/>
              </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/NCT01715298
org study id: CNVA237A2318
nct id: NCT01715298
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 in Standardized Area Under the Curve for Forced Expiratory Volume in One Second Post Dosing
time frame: Week 12
description: The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is measured at week 12 of treatment. Serial lung function measurements are taken at the following time points following dosing at week 12 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.
The primary endpoint was the change from baseline in FEV1 AUC0-12h following the morning dose at Week 12 (defined as the mean FEV1 change from baseline (CFB) over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur
measure: Change From Baseline in Standardized Area Under the Curve (AUC(0-12h)) for Forced Expiratory Volume in One Second Post Dosing
time frame: Day 1
description: The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1) post dosing (FEV1 AUC) is assessed at day 1 of treatment. Serial lung function measurements are taken at the following various time points post dosing at day 1 to calculate the FEV1 AUC: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.
.The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.
measure: Change From Baseline in Standardized Area Under The Curve for Forced Expiratory Volume in One Second for Different Time Spans Post Dosing
time frame: Day 1 and Week 12
description: The standardized Area Under the Curve (AUC) for Forced Expiratory Volume in one second (FEV1FEV1) is assessed for different time spans (0-4 h, 4-8 h, 8-12 h) 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 the following time points post dosing on day 1 and at week 12 to calculate the FEV1 AUC for these different time spans: .5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose.
The endpoint was the change from baseline (CFB) in FEV1 AUC0-12h following the morning dose at day 1 or week 12, respectively, (defined as the mean FEV1 change from baseline over 5 min to 11 h 55 mins divided by 11 h 50 mins). Where the FEV1 AUC is smaller than at baseline, a negative value can occur.
measure: Change From Baseline in Forced Expiratory Volume in One Second at All Individual Timepoints
time frame: Day 1 and week 12
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. Time points of the serial lung function measurements are 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. The table indicates the percent change from baseline (CFB) in FEV1 and standard deviation in brackets. Where the FEV1 is lower than at baseline, a negative percent value can occur.
measure: Mean Trough Forced Expiratory Volume in One Second
time frame: Day 1 and week 12
description: Mean trough Forced Expiratory Volume in one second (FEV1) is assessed as the arithmetic mean of two FEV1 measurements, conducted within the last hour of a 24 hour period from a morning dose, either that of day 1 or at week 12 of treatment. The data is reported as the change from baseline (CFB), with the baseline being the arithmetic mean of the two pre-dose measurements (-45 min and -15 min) preceding the serial lung function measurements on Day 1
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: Breathlessness Assessed by Transition Dyspnea Index
time frame: Week 12
description: Breathlessness at week 12 is measured using the interviewer-administered Transition Dyspnea Index (TDI). On day 1, breathlessness is assessed by the interviewer-administered Baseline Dyspnea Index (BDI). The change from BDI to TDI is assessed, with the TDI total score ranging from -9 to +9 units of the scale. The lower the score, the more deterioration in severity of dyspnea. Patients are considered to have clinically significant improvement (MCID) with the TDI score change versus BDI being equal to or greater than 1.
measure: Change From Baseline in Mean Number of Puffs of Rescue Medication Per Day
time frame: Baseline and week 12
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 change from baseline in the mean daily number of puffs used per patient over the 12 weeks treatment period. The baseline is calculated from the run-in epoch prior to randomization (mean number of puffs per day). A negative number indicates a reduction in the mean daily number of puffs of rescue medication.
measure: Change From Baseline in the Percentage of Days Without Rescue Medication Use
time frame: Baseline and week 12
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 change from baseline in the percentage of days without usage of rescue medication over the 12 weeks treatment period. The baseline is calculated as the percentage of days without usage of rescue medication from during the the run-in epoch prior to randomization.
measure: Change From Baseline in Daily Symptom Scores
time frame: day 1 to week 12
description: Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Symptom scores are calculated as the mean of the combined daily symptom scores (combined from morning and evening scores) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The change from baseline in the least squares mean daily symptom scores over the 12 week treatment period is provided. Where the mean daily symptom score over the 12 week treatment period is lower than the baseline, the result is negative. A negative result indicates an improvement in COPD symptom severity.
measure: Change From Baseline in the Percentage of Nights With "no Nighttime Awakenings"
time frame: Day 1 and week 12
description: Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the morning questionnaire relates to the number of awakenings due to COPD symptoms during the previous night. The answer with the lowest symptom score is "no waking due to symptoms." A night with "no nighttime awakening" is defined from diary data as any night where the patient did not wake up due to symptoms. The change from baseline in the percentage of nights with "no nighttime awakening" is calculated from the mean percentage of nights with this answer over the 12 week treatment period, with the baseline being The baseline is calculated from the run-in epoch prior to randomization.
measure: Change From Baseline in the Percentage of Days With "no Daytime Symptoms"
time frame: Day 1 to week 12
description: Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. 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 in the evening questionnaire. The change from baseline in the percentage of days with "no daytime symptoms" is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline being. The baseline is calculated from the run-in epoch prior to randomization.
measure: Change From Baseline in Percentage of "Days Able to Perform Usual Daily Activities"
time frame: Day 1 to week 12
description: Patients are reporting symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. One of the symptom questions of the evening questionnaire relates to the impact of COPD symptoms on the performance of usual daily activities ("Did your respiratory symptoms stop you performing your usual daily activities today"). The answer with the lowest symptom score is "not at all." 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. The change from baseline in the percentage of "days able to perform usual daily activities" is calculated from the mean percentage of days with this answer over the 12 week treatment period, with the baseline beingThe baseline is calculated from the run-in epoch prior to randomization.
measure: Change From Baseline in Forced Vital Capacity at All Individual Timepoints
time frame: Day 1 and week 12
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. Serial lung function measurements are taken at the following time points following dosing on Day 1 and at week 12: 5 min, 15 min, 1:00 h, 2:00 h, 4:00 h, 6:00 h, 8:00 h, and 11:55 h after the morning dose. For week 12 (day 85), the pre-dose measurements (-45 min and -15 min) and the trough measurements (23:15 h and 23:45 h post-dose) are included. The endpoints are the change from baseline in FVC following the morning dose on Day 1 and at Week 12. Where the FVC at any one timepoint is smaller than at baseline, a negative value can occur.
measure: Change From Baseline in Mean Trough Forced Vital Capacity
time frame: Day 1 and week 12
description: Mean trough Forced Vital Capacity (FVC) is assessed as the arithmetic mean of two FVC measurements, conducted within the last hour of a 24 hours period from a morning dose, either that of day 1 or at week 12 of treatment (23:15 h and 23:45 h assessments). The endpoints are the change from baseline in trough FVC on Day 1 and at Week 12, with the mean of the -45 min and -15 min measurements on Day 1 as the baseline.
measure: Change From Baseline in Morning and Nighttime Symptom Scores
time frame: Day 1 to week 12
description: Patients are reporting morning and nighttime symptoms by using an electronic diary. The electronic diary has 9 symptom questions each morning and each evening. Each question can be answered with one of four pre-defined answers, corresponding to a unit value of 0-3, where 0 stands for the lowest and 3 for the most severe symptom experience. Morning and nighttime symptoms scores for each patient over 12 weeks are reported and analyzed. Symptom scores are calculated as the mean of the symptom scores (morning symptom scores or nighttime symptom scores, respectively) for each patient over 12 weeks (Day 1 to week 12). The baseline is calculated from the run-in epoch prior to randomization. The outcome is calculated as the change from baseline in the morning and nighttime symptom scores, respectively. A negative number indicates a reduction in the symptom severity and is owed to the calculation of the change from baseline.
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 (Glycopyrronioum 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
participant flow: 
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outcome list: 
reported events: 
certain agreements: 
point of contact: 