<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT03034915</url>
  </required_header>
  <id_info>
    <org_study_id>201749</org_study_id>
    <secondary_id>2016-002513-22</secondary_id>
    <nct_id>NCT03034915</nct_id>
  </id_info>
  <brief_title>A 24-week Study to Compare Umeclidinium/Vilanterol (UMEC/VI), UMEC and Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>A 24-week Treatment, Multi-center, Randomized, Double-blind, Double-dummy, Parallel Group Study to Compare Umeclidinium/Vilanterol, Umeclidinium, and Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      COPD is characterized by an airflow limitation, which is not fully reversible, usually&#xD;
      progressive and accompanied by chronic cough, sputum production and dyspnea, which can be a&#xD;
      major cause of disability and anxiety associated with the disease. In addition, COPD is&#xD;
      associated with poor health-related quality of life (HRQoL). Pharmacologic therapy is used to&#xD;
      improve lung function, reduce symptoms, reduce the frequency and severity of exacerbations,&#xD;
      and also to improve health status and exercise tolerance.&#xD;
&#xD;
      This is a multi-center, randomized, double blind, double dummy, 3-arm parallel group study to&#xD;
      compare umeclidinium/vilanterol (62.5/25 microgram [mcg], once daily), umeclidinium (62.5&#xD;
      mcg, once daily), and salmeterol (50 mg, twice daily) in male and female subjects with COPD.&#xD;
      The primary purpose of this study is to demonstrate improvements in lung function for&#xD;
      subjects treated with UMEC/VI compared with UMEC for 24 weeks.&#xD;
&#xD;
      Approximately 2424 subjects will be randomized across 3 parallel arms in 1:1:1 ratio.&#xD;
      Subjects will be stratified based on long-acting bronchodilator usage during the run-in&#xD;
      period (none, one or 2 long-acting bronchodilators per day). Subjects will receive either&#xD;
      UMEC/VI inhalation powder (62.5/25 microgram [mcg] once daily) administered via the ELLIPTA®&#xD;
      dry powder inhaler (DPI) and placebo twice daily via DISKUS® DPI; or UMEC (62.5 mcg once&#xD;
      daily) administered via the ELLIPTA DPI and placebo twice daily via DISKUS DPI or salmeterol&#xD;
      (50 mcg twice daily [BID]) administered via the DISKUS DPI and placebo once daily via ELLIPTA&#xD;
      DPI. The duration of the study will be 29 to 31 weeks including a pre-screening period of 2&#xD;
      weeks, run-in period of 4 weeks, treatment period of 24 weeks and follow-up period of 1 week.&#xD;
&#xD;
      ELLIPTA and DISKUS are trademarks of GSK group of companies.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 16, 2017</start_date>
  <completion_date type="Actual">June 18, 2018</completion_date>
  <primary_completion_date type="Actual">June 18, 2018</primary_completion_date>
  <phase>Phase 4</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24</measure>
    <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
    <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of TDI Responders According to SAC TDI Focal Score</measure>
    <time_frame>Week 24</time_frame>
    <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score</measure>
    <time_frame>Baseline (Pre-dose on Day 1) and Week 21 to Week 24</time_frame>
    <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change From Baseline in E-RS Subscale Score</measure>
    <time_frame>Baseline (Pre-dose on Day 1) and Week 21 to Week 24</time_frame>
    <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of E-RS Responders According to E-RS Total Score</measure>
    <time_frame>Week 21 to Week 24</time_frame>
    <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score</measure>
    <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
    <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score</measure>
    <time_frame>Week 24</time_frame>
    <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in COPD Assessment Test (CAT)</measure>
    <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
    <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Responders According to CAT</measure>
    <time_frame>Week 24</time_frame>
    <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of &gt;=2 below Baseline. Non response was defined as CAT score &lt;2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)</measure>
    <time_frame>Up to Week 24</time_frame>
    <description>An AE is any untoward medical occurrence in a participant or clinical investigation participant , temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">2696</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be instructed to self-administer one dose of UMEC/VI 62.5/25 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be instructed to self-administer one dose of UMEC 62.5 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be instructed to self-administer one dose of salmeterol 50 mcg twice daily (morning and evening) via DISKUS DPI and placebo once daily morning via ELLIPTA DPI.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>UMEC/VI 62.5/25 mcg via ELLIPTA</intervention_name>
    <description>ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; the first strip contains umeclidinium bromide (62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate and second strip contains vilanterol trifenatae (25 mcg per blister) blended with lactose monohydrate and magnesium stearate.</description>
    <arm_group_label>UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>UMEC 62.5 mcg via ELLIPTA</intervention_name>
    <description>The ELLIPTA inhaler will contain one blister strip, which will have 30 blisters of umeclidinium bromide (62.5 mcg).</description>
    <arm_group_label>UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol 50 mcg via DISKUS</intervention_name>
    <description>The DISKUS inhaler will contain one blister strip, which will have 60 blisters of salmeterol xinafoate (50 mcg). The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.</description>
    <arm_group_label>Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo via ELLIPTA</intervention_name>
    <description>Lactose dry powder will be administered using ELLIPTA for both treatment periods. ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; containing lactose dry powder.</description>
    <arm_group_label>Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo via DISKUS</intervention_name>
    <description>Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.</description>
    <arm_group_label>UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
    <arm_group_label>UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  40 years or older at date of signing informed consent at Screening Visit 1&#xD;
&#xD;
          -  Outpatient with a diagnosis of COPD&#xD;
&#xD;
          -  Persistent airflow limitations as indicated by a pre and post-albuterol/salbutamol&#xD;
             FEV1/FVC ratio of &lt;0.70 and a post-albuterol/salbutamol FEV1 of &gt;=30% to &lt;=80%&#xD;
             predicted normal values at Screening Visit 1.&#xD;
&#xD;
          -  A CAT score of &gt;=10 at Screening Visit 1&#xD;
&#xD;
          -  Current or former cigarette smokers with a history of cigarette smoking of &gt;=10&#xD;
             pack-years (number of pack years = [number of cigarettes per day / 20] multiplied by&#xD;
             number of years smoked [e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per&#xD;
             day for 20 years both equal 10 pack-years]). Former smokers are defined as those who&#xD;
             have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use&#xD;
             cannot be used to calculate pack-year history.&#xD;
&#xD;
          -  Male and female subjects are eligible to participate in the study. A female subject is&#xD;
             eligible to participate if she is not pregnant (as confirmed by a negative urine human&#xD;
             chorionic gonadotrophin test), not lactating, and at least one of the following&#xD;
             conditions applies: non-reproductive potential defined as pre-menopausal females with&#xD;
             documented tubal ligation or documented hysteroscopic tubal occlusion procedure with&#xD;
             follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented&#xD;
             bilateral oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea.&#xD;
             In questionable cases, a blood sample with simultaneous follicle stimulating hormone&#xD;
             and estradiol levels consistent with menopause must be tested. Females on hormone&#xD;
             replacement therapy (HRT) and whose menopausal status is in doubt will be required to&#xD;
             use one of the highly effective contraception methods if they wish to continue their&#xD;
             HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of&#xD;
             post-menopausal status prior to study enrolment.&#xD;
&#xD;
        A female subject with reproductive potential is eligible to participate if she is not&#xD;
        pregnant and agrees to follow one of the highly effective methods for avoiding pregnancy in&#xD;
        females of reproductive potential from 30 days prior to the first dose of study medication&#xD;
        and until (at least five terminal half-lives or until any continuing pharmacologic effect&#xD;
        has ended, whichever is longer) after the last dose of study medication and completion of&#xD;
        the follow-up visit. The investigator is responsible for ensuring that subjects understand&#xD;
        how to properly use methods of contraception.&#xD;
&#xD;
          -  Capable of giving signed informed consent prior to study participation.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          -  A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if&#xD;
             they have a current diagnosis of COPD, which is the primary cause of their respiratory&#xD;
             symptoms).&#xD;
&#xD;
          -  Subjects with known alpha-antitrypsin deficiency as the underlying cause of COPD&#xD;
&#xD;
          -  Subjects with active tuberculosis are excluded. Subjects with other respiratory&#xD;
             disorders (e.g., clinically significant: bronchiectasis, sarcoidosis, lung fibrosis,&#xD;
             pulmonary hypertension, interstitial lung diseases) are excluded if these conditions&#xD;
             are the primary cause of their respiratory symptoms.&#xD;
&#xD;
          -  Current active liver or biliary disease (with the exception of Gilbert's syndrome or&#xD;
             asymptomatic gallstones or otherwise stable chronic liver disease as per investigator&#xD;
             assessment); stable chronic liver disease should generally be defined by the absence&#xD;
             of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric&#xD;
             varices, or persistent jaundice, or cirrhosis; chronic stable hepatitis B and C (e.g.,&#xD;
             presence of hepatitis B surface antigen or positive hepatitis C antibody test result&#xD;
             or within 3 months prior to first dose of study treatment) are acceptable if subject&#xD;
             otherwise meets entry criteria.&#xD;
&#xD;
          -  Subjects with unstable or life threatening cardiac disease. The investigational&#xD;
             product should be used with caution in subjects with severe cardiovascular disease. In&#xD;
             the opinion of the investigator, use will only be considered if the benefit is likely&#xD;
             to outweigh the risk in conditions such as myocardial infarction or unstable angina in&#xD;
             the last 6 months, or unstable or life threatening cardiac arrhythmia requiring&#xD;
             intervention in the last 3 months, or New York Heart Association Class IV heart&#xD;
             failure.&#xD;
&#xD;
          -  The investigator will determine the clinical significance of each abnormal&#xD;
             electrocardiogram (ECG) finding in relation to the subject's medical history and&#xD;
             exclude subjects who would be at undue risk by participating in the trial. Subjects&#xD;
             with the following abnormalities are excluded from participation in the study: atrial&#xD;
             fibrillation with rapid ventricular rate &gt;120 beats per minute (bpm), sustained or&#xD;
             non-sustained ventricular tachycardia, second degree heart block Mobitz type II or&#xD;
             third degree heart block (unless pacemaker or defibrillator had been inserted).&#xD;
&#xD;
          -  Subjects with medical conditions such as narrow-angle glaucoma, urinary retention,&#xD;
             prostatic hypertrophy, or bladder neck obstruction will be excluded unless, in the&#xD;
             opinion of the study physician, the benefit outweighs the risk.&#xD;
&#xD;
          -  Any subject who is considered unlikely to survive the duration of the study period or&#xD;
             has any rapidly progressing disease or immediate life-threatening illness (e.g.,&#xD;
             cancer). In addition, any subject who has any other condition (e.g., neurological&#xD;
             condition) that is likely to affect respiratory function will not be included in the&#xD;
             study.&#xD;
&#xD;
          -  Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia&#xD;
             and/or moderate or severe COPD exacerbation that has not resolved at least 14 days&#xD;
             prior to Screening Visit 1and at least 30 days following the last dose of&#xD;
             oral/systemic corticosteroids (if applicable).&#xD;
&#xD;
          -  Subjects who had received inhaled corticosteroids (ICS) or ICS/ long-acting&#xD;
             beta-agonist for the treatment of COPD in the 6 weeks prior to Screening Visit1.&#xD;
&#xD;
          -  Subjects who had &gt;1 moderate exacerbation in the 12 months prior to Screening Visit 1,&#xD;
             or one severe exacerbation requiring hospitalization in the 12 months prior to&#xD;
             Screening Visit 1.&#xD;
&#xD;
          -  Other respiratory tract infections that have not resolved at least 7 days prior to&#xD;
             Screening Visit 1.&#xD;
&#xD;
          -  Subjects with lung volume reduction surgery (including procedures such as&#xD;
             endobronchial valves) within the 12 months prior to Screening Visit 1.&#xD;
&#xD;
          -  Use of long-term oxygen therapy described as resting oxygen therapy &gt;3 Liter&#xD;
             (L)/minute (min) at screening required to maintain adequate oxygenation (e.g., oxygen&#xD;
             saturation in arterial blood [SaO2] &gt;90%; oxygen use &lt;=3 L/min flow is not&#xD;
             exclusionary, and subjects may adjust oxygen levels up or down as needed during the&#xD;
             study.)&#xD;
&#xD;
          -  Use of ICS within 6 weeks prior to Screening Visit 1; use of depot corticosteroids&#xD;
             within 12 weeks prior to Screening Visit 1; use of systemic, oral or parenteral&#xD;
             corticosteroids within 6 weeks prior to Screening Visit 1 (Localized corticosteroid&#xD;
             injections [e.g., intra-articular and epidural] are permitted); use of antibiotics&#xD;
             (for lower respiratory tract infection) within 6 weeks prior to Screening Visit 1; use&#xD;
             of phosphodiesterase 4 (PDE4) inhibitor (e.g., roflumilast) within 14 days prior to&#xD;
             Screening Visit 1; use of long-acting beta-agonist/ ICS combination products within 6&#xD;
             weeks prior to Screening Visit 1; use of theophyllines within 48 hours prior to&#xD;
             Screening Visit 1; use of oral long-acting beta2-agonists within 48 hours and&#xD;
             short-acting beta2-agonists within 12 hours prior to Screening Visit 1; use of inhaled&#xD;
             short-acting beta2-agonists within 4 hours prior to Screening Visit 1 (use of study&#xD;
             provided albuterol/salbutamol is permitted during the study, except in the 4-hour&#xD;
             period prior to spirometry testing); use of inhaled short-acting anticholinergics&#xD;
             within 4 hours prior to Screening Visit 1; use of inhaled short-acting&#xD;
             anticholinergic/short-acting beta2-agonist combination products within 4 hours prior&#xD;
             to Screening Visit 1; use of any other investigational medication within 30 days or&#xD;
             within 5 drug half-lives (whichever is longer) prior to Screening Visit 1.&#xD;
&#xD;
          -  Subject unable to withhold albuterol/salbutamol for the 4-hour period required prior&#xD;
             to spirometry testing at each study visit.&#xD;
&#xD;
          -  Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting&#xD;
             bronchodilators (e.g., albuterol/salbutamol).&#xD;
&#xD;
          -  A known or suspected history of alcohol or drug abuse within 2 years prior to&#xD;
             Screening Visit 1 that in the opinion of the investigator would prevent the subject&#xD;
             from completing the study procedures.&#xD;
&#xD;
          -  Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor&#xD;
             antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.&#xD;
&#xD;
          -  Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks&#xD;
             prior to Screening Visit 1. Subjects who are in the maintenance phase of a pulmonary&#xD;
             rehabilitation program are not excluded.&#xD;
&#xD;
          -  Subject is an investigator, sub-investigator, study coordinator, employee of a&#xD;
             participating investigator or study site, or immediate family member of the&#xD;
             aforementioned that is involved in this study.&#xD;
&#xD;
          -  In the opinion of the investigator, any subject who is unable to read and/or would not&#xD;
             be able to complete questionnaires on the electronic diary.&#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>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85018</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lincoln</city>
        <state>California</state>
        <zip>95648</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32825</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>O'Fallon</city>
        <state>Illinois</state>
        <zip>62269</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Natchitoches</city>
        <state>Louisiana</state>
        <zip>71457</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fridley</city>
        <state>Minnesota</state>
        <zip>55432</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <zip>55125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <zip>63017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint Charles</city>
        <state>Missouri</state>
        <zip>63301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Charlotte</city>
        <state>North Carolina</state>
        <zip>28207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Monroe</city>
        <state>North Carolina</state>
        <zip>28112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mooresville</city>
        <state>North Carolina</state>
        <zip>28117</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Anderson</city>
        <state>South Carolina</state>
        <zip>29621</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406-7108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lancaster</city>
        <state>South Carolina</state>
        <zip>29720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Seneca</city>
        <state>South Carolina</state>
        <zip>29678</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Union</city>
        <state>South Carolina</state>
        <zip>29379</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Sherman</city>
        <state>Texas</state>
        <zip>75092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Abingdon</city>
        <state>Virginia</state>
        <zip>24210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <state>Buenos Aires</state>
        <zip>C1028AAP</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <state>Buenos Aires</state>
        <zip>C1414AIF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <state>Buenos Aires</state>
        <zip>C1425AGC</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Florida</city>
        <state>Buenos Aires</state>
        <zip>1602</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lobos</city>
        <state>Buenos Aires</state>
        <zip>7240</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>7600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>B7600FZN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Paraná</city>
        <state>Buenos Aires</state>
        <zip>E3100BHK</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Quilmes</city>
        <state>Buenos Aires</state>
        <zip>B1878FNR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Vicente Lopez</city>
        <state>Buenos Aires</state>
        <zip>B1602DOH</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cordoba</city>
        <state>Córdova</state>
        <zip>X5003DCE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Concepcion del Uruguay</city>
        <state>Entre Ríos</state>
        <zip>3260</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Rafael</city>
        <state>Mendoza</state>
        <zip>5600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>2000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>S2002OJN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1120AAC</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1424BSF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Buenos Aires</city>
        <zip>C1425BEN</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Capital Federal</city>
        <zip>C1440BRR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autonoma de Buenis Aires</city>
        <zip>C1015ABR</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autónoma de Buenos Aires</city>
        <zip>C1121ABE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autónoma de Buenos Aires</city>
        <zip>C1128AAF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ciudad Autónoma de Buenos Aires</city>
        <zip>C1426ABP</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mendoza</city>
        <zip>5500</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mendoza</city>
        <zip>5501</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mendoza</city>
        <zip>M5500CCG</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Monte Grande</city>
        <zip>1842</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Miguel de Tucumán</city>
        <zip>4000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santa Fe</city>
        <zip>3000</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santa Rosa</city>
        <zip>6300</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tucumán</city>
        <zip>T4000DGF</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Coffs Harbour</city>
        <state>New South Wales</state>
        <zip>2450</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Darlinghurst, Sydney</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kanwal</city>
        <state>New South Wales</state>
        <zip>2259</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Port Macquarie</city>
        <state>New South Wales</state>
        <zip>2444</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moncton</city>
        <state>New Brunswick</state>
        <zip>E1G1A7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Truro</city>
        <state>Nova Scotia</state>
        <zip>B2N 1L2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8L 5G8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N5W 6A2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Sarnia</city>
        <state>Ontario</state>
        <zip>N7T 4X3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M9V 4B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Windsor</city>
        <state>Ontario</state>
        <zip>N8X 1T3</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gatineau</city>
        <state>Quebec</state>
        <zip>J8Y 6S8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mirabel</city>
        <state>Quebec</state>
        <zip>J7J 2K8</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <zip>H1M 1B1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St. Charles-Borromee</city>
        <state>Quebec</state>
        <zip>J6E 2B4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Quebec</city>
        <zip>G1V 4G5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Quebec</city>
        <zip>G1W 4R4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Marseille cedex 03</city>
        <zip>13331</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nice</city>
        <zip>06000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Perpignan</city>
        <zip>66000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pessac cedex</city>
        <zip>33604</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Karlsruhe</city>
        <state>Baden-Wuerttemberg</state>
        <zip>76137</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Wiesloch</city>
        <state>Baden-Wuerttemberg</state>
        <zip>69168</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bamberg</city>
        <state>Bayern</state>
        <zip>96049</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Erlangen</city>
        <state>Bayern</state>
        <zip>91052</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Muenchen</city>
        <state>Bayern</state>
        <zip>80339</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Muenchen</city>
        <state>Bayern</state>
        <zip>81241</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Potsdam</city>
        <state>Brandenburg</state>
        <zip>14469</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ruedersdorf</city>
        <state>Brandenburg</state>
        <zip>15562</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Darmstadt</city>
        <state>Hessen</state>
        <zip>64283</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt am Main</city>
        <state>Hessen</state>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60389</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <state>Hessen</state>
        <zip>60596</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fulda</city>
        <state>Hessen</state>
        <zip>36039</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kassel</city>
        <state>Hessen</state>
        <zip>34121</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Marburg</city>
        <state>Hessen</state>
        <zip>35037</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Neu isenburg</city>
        <state>Hessen</state>
        <zip>63263</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Schwerin</city>
        <state>Mecklenburg-Vorpommern</state>
        <zip>19055</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30159</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30173</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Osnabrueck</city>
        <state>Niedersachsen</state>
        <zip>49074</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Peine</city>
        <state>Niedersachsen</state>
        <zip>31224</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Wardenburg</city>
        <state>Niedersachsen</state>
        <zip>26203</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bergisch Gladbach</city>
        <state>Nordrhein-Westfalen</state>
        <zip>51429</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bochum</city>
        <state>Nordrhein-Westfalen</state>
        <zip>44787</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bonn</city>
        <state>Nordrhein-Westfalen</state>
        <zip>53119</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bonn</city>
        <state>Nordrhein-Westfalen</state>
        <zip>53123</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Dortmund</city>
        <state>Nordrhein-Westfalen</state>
        <zip>44263</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Dueren</city>
        <state>Nordrhein-Westfalen</state>
        <zip>52349</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Essen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45355</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Essen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45359</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gelsenkirchen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45879</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Koeln</city>
        <state>Nordrhein-Westfalen</state>
        <zip>51069</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rheine</city>
        <state>Nordrhein-Westfalen</state>
        <zip>48431</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Warendorf</city>
        <state>Nordrhein-Westfalen</state>
        <zip>48231</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Koblenz</city>
        <state>Rheinland-Pfalz</state>
        <zip>56068</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Teuchern</city>
        <state>Sachsen-Anhalt</state>
        <zip>06682</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Annaberg</city>
        <state>Sachsen</state>
        <zip>09456</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Delitzsch</city>
        <state>Sachsen</state>
        <zip>04509</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Dresden</city>
        <state>Sachsen</state>
        <zip>01069</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzg</city>
        <state>Sachsen</state>
        <zip>04109</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04157</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04275</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04357</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mittweida</city>
        <state>Sachsen</state>
        <zip>09648</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Geesthacht</city>
        <state>Schleswig-Holstein</state>
        <zip>21502</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Luebeck</city>
        <state>Schleswig-Holstein</state>
        <zip>23552</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Schleswig</city>
        <state>Schleswig-Holstein</state>
        <zip>24837</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Schmoelln</city>
        <state>Thueringen</state>
        <zip>04626</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10119</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10367</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10625</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10717</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>10787</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>12627</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>13086</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>13156</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>14059</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <zip>60313</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>20253</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22143</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamburg</city>
        <zip>22299</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <zip>04207</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Benevento</city>
        <state>Campania</state>
        <zip>82100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Napoli</city>
        <state>Campania</state>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Salerno</city>
        <state>Campania</state>
        <zip>84131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Felice A Cancello (CE)</city>
        <state>Campania</state>
        <zip>81027</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Reggio Emilia</city>
        <state>Emilia-Romagna</state>
        <zip>42100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Riccione (RN)</city>
        <state>Emilia-Romagna</state>
        <zip>47838</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pordenone</city>
        <state>Friuli-Venezia-Giulia</state>
        <zip>33170</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tradate (VA)</city>
        <state>Lombardia</state>
        <zip>21049</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cassano Delle Murge (BA)</city>
        <state>Puglia</state>
        <zip>70020</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Palermo</city>
        <state>Sicilia</state>
        <zip>90146</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56124</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Sisto (PG)</city>
        <state>Umbria</state>
        <zip>06156</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Napoli</city>
        <zip>80131</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Pietro Vernotico</city>
        <zip>72027</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44100</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Zapopan</city>
        <state>Jalisco</state>
        <zip>45070</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Almere</city>
        <zip>1311 RL</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Beek</city>
        <zip>6191 JW</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Breda</city>
        <zip>4818 CK</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Den Haag</city>
        <zip>2565 KV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Heerlen</city>
        <zip>6419 PC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hoorn</city>
        <zip>1624 NP</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kloosterhaar</city>
        <zip>7694 AC</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3067 GJ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Zutphen</city>
        <zip>7207 AE</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Eloffsdal</city>
        <state>Gauteng</state>
        <zip>0084</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2113</zip>
        <country>South Africa</country>
      </address>
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  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0087</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0121</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Middelburg</city>
        <state>Mpumalanga</state>
        <zip>1050</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bloemfontein</city>
        <zip>9301</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cape Town</city>
        <zip>7570</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Durban</city>
        <zip>4001</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mowbray</city>
        <zip>7700</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Panorama</city>
        <zip>7500</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Reiger Park</city>
        <zip>1459</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Marbella - Málaga</city>
        <state>Andalucia</state>
        <zip>29603</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Alicante</city>
        <zip>03004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Centelles (Barcelona)</city>
        <zip>08540</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gerona</city>
        <zip>17005</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mérida (Badajoz)</city>
        <zip>06800</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Peralada( Girona)</city>
        <zip>17491</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Borås</city>
        <zip>SE-506 30</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Göteborg</city>
        <zip>SE-413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Göteborg</city>
        <zip>SE-413 90</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Höllviken</city>
        <zip>SE-236 51</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Linköping</city>
        <zip>SE-587 58</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Luleå</city>
        <zip>SE-971 89</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lund</city>
        <zip>SE-221 85</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lund</city>
        <zip>SE-222 22</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Malmö</city>
        <zip>SE-211 52</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Skövde</city>
        <zip>SE-541 50</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Stockholm</city>
        <zip>11446</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Uppsala</city>
        <zip>SE-752 37</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Örebro</city>
        <zip>SE-703 62</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Canada</country>
    <country>France</country>
    <country>Germany</country>
    <country>Italy</country>
    <country>Mexico</country>
    <country>Netherlands</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Sweden</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Maltais F, Bjermer L, Kerwin EM, Jones PW, Watkins ML, Tombs L, Naya IP, Boucot IH, Lipson DA, Compton C, Vahdati-Bolouri M, Vogelmeier CF. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019 Oct 30;20(1):238. doi: 10.1186/s12931-019-1193-9.</citation>
    <PMID>31666084</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>January 25, 2017</study_first_submitted>
  <study_first_submitted_qc>January 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 27, 2017</study_first_posted>
  <results_first_submitted>June 16, 2019</results_first_submitted>
  <results_first_submitted_qc>June 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">July 15, 2019</results_first_posted>
  <last_update_submitted>March 2, 2020</last_update_submitted>
  <last_update_submitted_qc>March 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 11, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vilanterol</keyword>
  <keyword>COPD</keyword>
  <keyword>HRQoL</keyword>
  <keyword>Salmeterol</keyword>
  <keyword>Umeclidinium</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>Salmeterol Xinafoate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>IPD is available via the Clinical Study Data Request site (click on the link provided below)</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>https://clinicalstudydatarequest.com/Posting.aspx?ID=20277</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/15/NCT03034915/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/15/NCT03034915/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>In this randomized, double-blind, double dummy, 3-arm parallel group study, eligible participants received Umeclidinium/Vilanterol (UMEC/VI) 62.5/25 microgram (mcg) once daily via the ELLIPTA dry powder inhaler (DPI), or UMEC 62.5 mcg once daily via ELLIPTA DPI, or Salmeterol (SAL) 50 mcg twice daily (BID) via the DISKUS DPI (1:1:1) for 24 weeks.</recruitment_details>
      <pre_assignment_details>A total of 3591 participants who met the eligibility criteria were screened; 2431 participants were randomized and 2425 comprised the Intent to Treat (ITT) population (6 participants randomized in error and did not receive any treatment).The study consisted of a run-in period (4 weeks), treatment period (24 weeks) and follow up period (7+/-3 days).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
          <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="P2">
          <title>UMEC 62.5 mcg + Placebo</title>
          <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="P3">
          <title>Salmeterol 50 mcg+Placebo</title>
          <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="812"/>
                <participants group_id="P2" count="804"/>
                <participants group_id="P3" count="809"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="717"/>
                <participants group_id="P2" count="650"/>
                <participants group_id="P3" count="683"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
                <participants group_id="P2" count="154"/>
                <participants group_id="P3" count="126"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="32"/>
                <participants group_id="P3" count="22"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="13"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
                <participants group_id="P2" count="46"/>
                <participants group_id="P3" count="41"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="16"/>
                <participants group_id="P3" count="18"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Site closed</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol-defined withdrawal criteria met</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="29"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
          <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="B2">
          <title>UMEC 62.5 mcg + Placebo</title>
          <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="B3">
          <title>Salmeterol 50 mcg+Placebo</title>
          <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="812"/>
            <count group_id="B2" value="804"/>
            <count group_id="B3" value="809"/>
            <count group_id="B4" value="2425"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.6" spread="8.37"/>
                    <measurement group_id="B2" value="64.9" spread="8.48"/>
                    <measurement group_id="B3" value="64.4" spread="8.53"/>
                    <measurement group_id="B4" value="64.6" spread="8.46"/>
                  </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="319"/>
                    <measurement group_id="B2" value="327"/>
                    <measurement group_id="B3" value="342"/>
                    <measurement group_id="B4" value="988"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="493"/>
                    <measurement group_id="B2" value="477"/>
                    <measurement group_id="B3" value="467"/>
                    <measurement group_id="B4" value="1437"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="72"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian - Central/South Asian Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian - Japanese Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian - East Asian Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White - Arabic/North African Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White - White/Caucasian/European Heritage</title>
                  <measurement_list>
                    <measurement group_id="B1" value="764"/>
                    <measurement group_id="B2" value="763"/>
                    <measurement group_id="B3" value="765"/>
                    <measurement group_id="B4" value="2292"/>
                  </measurement_list>
                </category>
                <category>
                  <title>American Indian or Alaska Native &amp; White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American &amp; White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or other Pacific Islander &amp; White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24</title>
        <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.</description>
        <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24</title>
          <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</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="691"/>
                <count group_id="O2" value="621"/>
                <count group_id="O3" value="654"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.122" spread="0.0081"/>
                    <measurement group_id="O2" value="0.056" spread="0.0085"/>
                    <measurement group_id="O3" value="-0.019" spread="0.0083"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.066</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0118</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.043</ci_lower_limit>
            <ci_upper_limit>0.089</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.141</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0117</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.118</ci_lower_limit>
            <ci_upper_limit>0.164</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.075</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.0119</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.051</ci_lower_limit>
            <ci_upper_limit>0.098</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24</title>
        <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24</title>
          <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="704"/>
                <count group_id="O2" value="636"/>
                <count group_id="O3" value="673"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.68" spread="0.109"/>
                    <measurement group_id="O2" value="1.30" spread="0.114"/>
                    <measurement group_id="O3" value="1.22" spread="0.111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.018</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.37</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.157</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.06</ci_lower_limit>
            <ci_upper_limit>0.68</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.004</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.45</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.155</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.15</ci_lower_limit>
            <ci_upper_limit>0.76</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.610</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.08</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.159</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.23</ci_lower_limit>
            <ci_upper_limit>0.39</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 24</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of TDI Responders According to SAC TDI Focal Score</title>
        <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of TDI Responders According to SAC TDI Focal Score</title>
          <description>TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="806"/>
                <count group_id="O2" value="799"/>
                <count group_id="O3" value="807"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50"/>
                    <measurement group_id="O2" value="42"/>
                    <measurement group_id="O3" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.43</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.17</ci_lower_limit>
            <ci_upper_limit>1.75</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI vs UMEC at Week 24</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.21</ci_lower_limit>
            <ci_upper_limit>1.81</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.755</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.84</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score</title>
        <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
        <time_frame>Baseline (Pre-dose on Day 1) and Week 21 to Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score</title>
          <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="677"/>
                <count group_id="O2" value="621"/>
                <count group_id="O3" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.52" spread="0.148"/>
                    <measurement group_id="O2" value="-0.99" spread="0.152"/>
                    <measurement group_id="O3" value="-0.69" spread="0.150"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.013</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.53</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.213</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.95</ci_lower_limit>
            <ci_upper_limit>-0.11</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.83</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.211</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.25</ci_lower_limit>
            <ci_upper_limit>-0.42</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24..</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.159</p_value>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.30</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.214</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.72</ci_lower_limit>
            <ci_upper_limit>0.12</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change From Baseline in E-RS Subscale Score</title>
        <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
        <time_frame>Baseline (Pre-dose on Day 1) and Week 21 to Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change From Baseline in E-RS Subscale Score</title>
          <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="677"/>
                <count group_id="O2" value="621"/>
                <count group_id="O3" value="653"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>RS-BRL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.67" spread="0.080"/>
                    <measurement group_id="O2" value="-0.40" spread="0.082"/>
                    <measurement group_id="O3" value="-0.22" spread="0.081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RS-CSP</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.45" spread="0.044"/>
                    <measurement group_id="O2" value="-0.38" spread="0.045"/>
                    <measurement group_id="O3" value="-0.32" spread="0.044"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>RS-CSY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.39" spread="0.049"/>
                    <measurement group_id="O2" value="-0.22" spread="0.050"/>
                    <measurement group_id="O3" value="-0.15" spread="0.049"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.016</p_value>
            <p_value_desc>E-RS Breathlessness Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.27</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.114</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.50</ci_lower_limit>
            <ci_upper_limit>-0.05</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>E-RS Breathlessness Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.46</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.113</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.68</ci_lower_limit>
            <ci_upper_limit>-0.23</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.115</p_value>
            <p_value_desc>E-RS Breathlessness Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.18</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.115</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.41</ci_lower_limit>
            <ci_upper_limit>0.04</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.247</p_value>
            <p_value_desc>E-RS Cough and Sputum Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.063</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.20</ci_lower_limit>
            <ci_upper_limit>0.05</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.042</p_value>
            <p_value_desc>E-RS Cough and Sputum Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.13</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.063</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.25</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.391</p_value>
            <p_value_desc>E-RS Cough and Sputum Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.05</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.063</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.18</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.014</p_value>
            <p_value_desc>E-RS Chest Symptoms Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.17</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.070</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.31</ci_lower_limit>
            <ci_upper_limit>-0.04</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 21 to Week 24</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <p_value_desc>E-RS Chest Symptoms Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.24</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.069</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.37</ci_lower_limit>
            <ci_upper_limit>-0.10</ci_upper_limit>
            <estimate_desc>LS Mean difference comapring UMEC/VI versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.340</p_value>
            <p_value_desc>E-RS Chest Symptoms Score</p_value_desc>
            <method>Mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.07</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.070</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.20</ci_lower_limit>
            <ci_upper_limit>0.07</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of E-RS Responders According to E-RS Total Score</title>
        <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.</description>
        <time_frame>Week 21 to Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of E-RS Responders According to E-RS Total Score</title>
          <description>The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="809"/>
                <count group_id="O2" value="800"/>
                <count group_id="O3" value="808"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                    <measurement group_id="O2" value="27"/>
                    <measurement group_id="O3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.52</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.22</ci_lower_limit>
            <ci_upper_limit>1.89</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI vs UMEC at Week 21 to Week 24</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.53</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.23</ci_lower_limit>
            <ci_upper_limit>1.90</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.969</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.80</ci_lower_limit>
            <ci_upper_limit>1.26</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 21 to Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score</title>
        <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
        <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score</title>
          <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="704"/>
                <count group_id="O2" value="636"/>
                <count group_id="O3" value="674"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.98" spread="0.465"/>
                    <measurement group_id="O2" value="-5.23" spread="0.484"/>
                    <measurement group_id="O3" value="-3.29" spread="0.475"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.709</p_value>
            <method>mixed model repeated measure</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.25</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.672</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.07</ci_lower_limit>
            <ci_upper_limit>1.57</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.011</p_value>
            <method>mixed model repeated measure</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-1.69</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.665</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.99</ci_lower_limit>
            <ci_upper_limit>-0.39</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.004</p_value>
            <method>mixed model repeated measure</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-1.94</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.678</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.27</ci_lower_limit>
            <ci_upper_limit>-0.61</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score</title>
        <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score</title>
          <description>SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.</description>
          <population>ITT Population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="811"/>
                <count group_id="O2" value="802"/>
                <count group_id="O3" value="809"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="41"/>
                    <measurement group_id="O3" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.063</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.21</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.99</ci_lower_limit>
            <ci_upper_limit>1.48</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.49</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.22</ci_lower_limit>
            <ci_upper_limit>1.83</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.045</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.00</ci_lower_limit>
            <ci_upper_limit>1.51</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in COPD Assessment Test (CAT)</title>
        <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
        <time_frame>Baseline (Pre-dose on Day 1) and Week 24</time_frame>
        <population>ITT population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in COPD Assessment Test (CAT)</title>
          <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.</description>
          <population>ITT population. Participants represents those with data available at the time point being presented; however, all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.</population>
          <units>Scores on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="703"/>
                <count group_id="O2" value="633"/>
                <count group_id="O3" value="669"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.5" spread="0.21"/>
                    <measurement group_id="O2" value="-3.4" spread="0.22"/>
                    <measurement group_id="O3" value="-2.9" spread="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.891</p_value>
            <method>mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.30</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.6</ci_lower_limit>
            <ci_upper_limit>0.6</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.074</p_value>
            <method>mixed model repeated measures</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.30</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.1</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.107</p_value>
            <method>mixed model repeated measures</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>-0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.31</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.1</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
            <estimate_desc>LS Mean difference comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Responders According to CAT</title>
        <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of &gt;=2 below Baseline. Non response was defined as CAT score &lt;2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.</description>
        <time_frame>Week 24</time_frame>
        <population>ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Responders According to CAT</title>
          <description>The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of &gt;=2 below Baseline. Non response was defined as CAT score &lt;2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.</description>
          <population>ITT Population.</population>
          <units>Percentage of responders</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="812"/>
                <count group_id="O2" value="804"/>
                <count group_id="O3" value="809"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="48"/>
                    <measurement group_id="O3" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.35</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.11</ci_lower_limit>
            <ci_upper_limit>1.65</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus UMEC at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.037</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.01</ci_lower_limit>
            <ci_upper_limit>1.50</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC/VI versus salmeterol at Week 24.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.363</p_value>
            <method>generalized linear mixed model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.91</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.75</ci_lower_limit>
            <ci_upper_limit>1.11</ci_upper_limit>
            <estimate_desc>Odds Ratio (responder vs. a non-responder) comparing UMEC versus salmeterol at Week 24.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)</title>
        <description>An AE is any untoward medical occurrence in a participant or clinical investigation participant , temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.</description>
        <time_frame>Up to Week 24</time_frame>
        <population>ITT Population.</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
            <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O2">
            <title>UMEC 62.5 mcg + Placebo</title>
            <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
          <group group_id="O3">
            <title>Salmeterol 50 mcg+Placebo</title>
            <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)</title>
          <description>An AE is any untoward medical occurrence in a participant or clinical investigation participant , temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.</description>
          <population>ITT Population.</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="812"/>
                <count group_id="O2" value="804"/>
                <count group_id="O3" value="809"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="315"/>
                    <measurement group_id="O2" value="316"/>
                    <measurement group_id="O3" value="314"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Any SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49"/>
                    <measurement group_id="O2" value="35"/>
                    <measurement group_id="O3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On-Treatment serious adverse events (SAEs) and non-serious AEs (nSAEs) were collected from start of study treatment until Week 24.</time_frame>
      <desc>On-Treatment SAEs and nSAEs were reported for ITT Population.</desc>
      <group_list>
        <group group_id="E1">
          <title>UMEC/VI 62.5/25 mcg+ Placebo</title>
          <description>Participants with COPD received UMEC/VI 62.5/25 mcg once daily via the ELLIPTA DPI along with placebo twice daily via the DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="E2">
          <title>UMEC 62.5 mcg + Placebo</title>
          <description>Participants with COPD received UMEC 62.5mcg once daily via the ELLIPTA DPI along with placebo twice daily via DISKUS DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
        <group group_id="E3">
          <title>Salmeterol 50 mcg+Placebo</title>
          <description>Participants with COPD received salmeterol 50 mcg twice daily via the DISKUS DPI along with placebo once daily via ELLIPTA DPI for 24 weeks. In addition albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the study. Participants were followed up 7 days after the last dose of study medication.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="812"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="804"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="49" subjects_at_risk="812"/>
                <counts group_id="E2" subjects_affected="35" subjects_at_risk="804"/>
                <counts group_id="E3" subjects_affected="38" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Microcytic anaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Splenic infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="812"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Cardio-respiratory arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Atrioventricular block complete</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Duodenal ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Enteritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Enterocolitis haemorrhagic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Femoral hernia strangulated</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Gastric polyps</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Gastric ulcer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Gastrooesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="812"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="804"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Appendicitis perforated</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Bacterial colitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Encephalitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Infective exacerbation of chronic obstructive airways disease</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Muscle abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Pyelonephritis acute</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Septic shock</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Craniocerebral injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Fibula fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Humerus fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Post-thoracotomy pain syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Tendon rupture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Vascular pseudoaneurysm</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rotator cuff syndrome</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Spinal pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Synovial cyst</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Bladder neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Small cell lung cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of lung</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Adenocarcinoma of colon</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Adenosquamous cell lung cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Benign lung neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Lung neoplasm malignant</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Malignant melanoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Meningioma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Non-small cell lung cancer metastatic</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Papillary cystadenoma lymphomatosum</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Prostate cancer</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Basilar artery stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Brain stem stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Cerebellar infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Encephalopathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Status epilepticus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Tethered cord syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </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" events="7" subjects_affected="7" subjects_at_risk="812"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="804"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Lung infiltration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral arterial occlusive disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Haematoma</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Aortic stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Hypertensive emergency</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Subclavian artery stenosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="809"/>
              </event>
              <event>
                <sub_title>Varicose vein</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="812"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="804"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA 21.0</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="68" subjects_at_risk="812"/>
                <counts group_id="E2" subjects_affected="87" subjects_at_risk="804"/>
                <counts group_id="E3" subjects_affected="84" subjects_at_risk="809"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="81" subjects_affected="68" subjects_at_risk="812"/>
                <counts group_id="E2" events="103" subjects_affected="87" subjects_at_risk="804"/>
                <counts group_id="E3" events="94" subjects_affected="84" subjects_at_risk="809"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.com</email>
    </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/NCT03034915
org study id: 201749
secondary id: 2016-002513-22
nct id: NCT03034915
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
COPD is characterized by an airflow limitation, which is not fully reversible, usually
      progressive and accompanied by chronic cough, sputum production and dyspnea, which can be a
      major cause of disability and anxiety associated with the disease. In addition, COPD is
      associated with poor health-related quality of life (HRQoL). Pharmacologic therapy is used to
      improve lung function, reduce symptoms, reduce the frequency and severity of exacerbations,
      and also to improve health status and exercise tolerance.

      This is a multi-center, randomized, double blind, double dummy, 3-arm parallel group study to
      compare umeclidinium/vilanterol (62.5/25 microgram [mcg], once daily), umeclidinium (62.5
      mcg, once daily), and salmeterol (50 mg, twice daily) in male and female subjects with COPD.
      The primary purpose of this study is to demonstrate improvements in lung function for
      subjects treated with UMEC/VI compared with UMEC for 24 weeks.

      Approximately 2424 subjects will be randomized across 3 parallel arms in 1:1:1 ratio.
      Subjects will be stratified based on long-acting bronchodilator usage during the run-in
      period (none, one or 2 long-acting bronchodilators per day). Subjects will receive either
      UMEC/VI inhalation powder (62.5/25 microgram [mcg] once daily) administered via the ELLIPTA®
      dry powder inhaler (DPI) and placebo twice daily via DISKUS® DPI; or UMEC (62.5 mcg once
      daily) administered via the ELLIPTA DPI and placebo twice daily via DISKUS DPI or salmeterol
      (50 mcg twice daily [BID]) administered via the DISKUS DPI and placebo once daily via ELLIPTA
      DPI. The duration of the study will be 29 to 31 weeks including a pre-screening period of 2
      weeks, run-in period of 4 weeks, treatment period of 24 weeks and follow-up period of 1 week.

      ELLIPTA and DISKUS are trademarks of GSK group of companies.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24
time frame: Baseline (Pre-dose on Day 1) and Week 24
description: FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.
measure: Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24
time frame: Week 24
description: TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.
measure: Percentage of TDI Responders According to SAC TDI Focal Score
time frame: Week 24
description: TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.
measure: Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score
time frame: Baseline (Pre-dose on Day 1) and Week 21 to Week 24
description: The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.
measure: Mean Change From Baseline in E-RS Subscale Score
time frame: Baseline (Pre-dose on Day 1) and Week 21 to Week 24
description: The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.
measure: Percentage of E-RS Responders According to E-RS Total Score
time frame: Week 21 to Week 24
description: The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.
measure: Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score
time frame: Baseline (Pre-dose on Day 1) and Week 24
description: SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.
measure: Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score
time frame: Week 24
description: SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.
measure: Change From Baseline in COPD Assessment Test (CAT)
time frame: Baseline (Pre-dose on Day 1) and Week 24
description: The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.
measure: Percentage of Responders According to CAT
time frame: Week 24
description: The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of >=2 below Baseline. Non response was defined as CAT score <2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.
measure: Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)
time frame: Up to Week 24
description: An AE is any untoward medical occurrence in a participant or clinical investigation participant , temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.
arm group label: UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS
arm group type: Experimental
description: Subjects will be instructed to self-administer one dose of UMEC/VI 62.5/25 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.
arm group label: UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS
arm group type: Experimental
description: Subjects will be instructed to self-administer one dose of UMEC 62.5 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.
arm group label: Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA
arm group type: Experimental
description: Subjects will be instructed to self-administer one dose of salmeterol 50 mcg twice daily (morning and evening) via DISKUS DPI and placebo once daily morning via ELLIPTA DPI.
intervention type: Drug
intervention name: UMEC/VI 62.5/25 mcg via ELLIPTA
description: ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; the first strip contains umeclidinium bromide (62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate and second strip contains vilanterol trifenatae (25 mcg per blister) blended with lactose monohydrate and magnesium stearate.
arm group label: UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS
intervention type: Drug
intervention name: UMEC 62.5 mcg via ELLIPTA
description: The ELLIPTA inhaler will contain one blister strip, which will have 30 blisters of umeclidinium bromide (62.5 mcg).
arm group label: UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS
intervention type: Drug
intervention name: Salmeterol 50 mcg via DISKUS
description: The DISKUS inhaler will contain one blister strip, which will have 60 blisters of salmeterol xinafoate (50 mcg). The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.
arm group label: Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA
intervention type: Drug
intervention name: Placebo via ELLIPTA
description: Lactose dry powder will be administered using ELLIPTA for both treatment periods. ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; containing lactose dry powder.
arm group label: Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA
intervention type: Drug
intervention name: Placebo via DISKUS
description: Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.
arm group label: UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS
arm group label: UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
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country: Argentina
country: Australia
country: Canada
country: France
country: Germany
country: Italy
country: Mexico
country: Netherlands
country: South Africa
country: Spain
country: Sweden
country: United States
citation: Maltais F, Bjermer L, Kerwin EM, Jones PW, Watkins ML, Tombs L, Naya IP, Boucot IH, Lipson DA, Compton C, Vahdati-Bolouri M, Vogelmeier CF. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019 Oct 30;20(1):238. doi: 10.1186/s12931-019-1193-9.
PMID: 31666084
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Salmeterol Xinafoate
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd time frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
ipd url: https://clinicalstudydatarequest.com/Posting.aspx?ID=20277
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 