<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02257385</url>
  </required_header>
  <id_info>
    <org_study_id>116961</org_study_id>
    <nct_id>NCT02257385</nct_id>
  </id_info>
  <brief_title>Comparative Study of Umeclidinium/Vilanterol (UMEC/VI) in a Fixed Dose Combination With Indacaterol Plus Tiotropium</brief_title>
  <official_title>Study DB2116961, A Multicentre, Randomised, Blinded, Parallel Group Study to Compare UMEC/VI (Umeclidinium/Vilanterol) in a Fixed Dose Combination With Indacaterol Plus Tiotropium in Symptomatic Subjects With Moderate to Very Severe 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to&#xD;
      evaluate the efficacy and safety of UMEC/VI inhalation powder (62.5/25 microgram [mcg] Once&#xD;
      daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol&#xD;
      plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a&#xD;
      treatment period of 12 weeks in participants with moderate to very severe Chronic Obstructive&#xD;
      Pulmonary Disease (COPD). The purpose of this study is to demonstrate that UMEC/VI (delivered&#xD;
      via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD participants, is&#xD;
      non-inferior to the combination of indacaterol (delivered via BREEZHALER® inhaler) plus&#xD;
      tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced expiratory volume&#xD;
      in one second (FEV1) after 12 weeks of treatment. Participants who met the eligibility&#xD;
      criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior to&#xD;
      randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and week&#xD;
      12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study&#xD;
      participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK&#xD;
      group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH&#xD;
      &amp; Co. KG. BREEZHALER is a registered trademark of Novartis AG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2014</start_date>
  <completion_date type="Actual">May 4, 2015</completion_date>
  <primary_completion_date type="Actual">May 4, 2015</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Treatment Day 85 (Visit 8)</measure>
    <time_frame>Baseline (BL) and Day 85</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 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84</measure>
    <time_frame>Baseline and Day 84</time_frame>
    <description>BL FEV1 was the mean of the 2 assessments made 30 and 5 min PD on Day 1. WM FEV1 derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1 and 84 using the 0-6 hr post-dose FEV1 measurements collected on that day, which included PD FEV1 (taken 30 and 5 min prior to dosing on Day 1 and the 30 and 5 min reading prior to dosing on Day 84) and post-dose FEV1 measurements at 1, 3 and 6 hr post-dose.WM change from BL was the WM at at the visit minus the BL value. Analysis was performed using a RM model with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1) center group, day, day by BL and day by trt interaction, where day was nominal. Only par with data available at the specified TP were analyzed but all par w/o missing covariate information and with &gt;=1 post-BL measurement were included in the analysis.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">967</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>UMEC/VI arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be instructed to self-administer one dose each morning of UMEC/VI Inhalation Powder 62.5/25 mcg once daily via ELLIPTA DPI, placebo once daily via HANDIHALER inhaler and placebo once daily via BREEZHALER inhaler</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be instructed to self-administer one dose each morning of Tiotropium bromide 18 mcg once daily via HANDIHALER inhaler, Indacaterol 150 mcg once daily via BREEZHALER inhaler and placebo once daily via ELLIPTA DPI</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>UMEC/VI</intervention_name>
    <description>ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains Umeclidinium bromide (unit dose strengths 62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate 0.6% weight/weight (w/w) of total drug product and second strip contains Vilanterol (unit dose strengths 25 mcg per blister) blended with lactose monohydrate and magnesium stearate 1.0% w/w of total drug product</description>
    <arm_group_label>UMEC/VI arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>UMEC/VI matching placebo</intervention_name>
    <description>ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains lactose monohydrate and magnesium stearate 0.6% w/w of total drug product and second strip contains lactose monohydrate and magnesium stearate 1.0% w/w of total drug product</description>
    <arm_group_label>UMEC/VI arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>Tiotropium (as bromide monohydrate) inhalation capsules 18 mcg per dose will be supplied along with HANDIHALER inhalers manufactured by Boehringer Ingelheim</description>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium matching placebo</intervention_name>
    <description>Tiotropium matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with HANDIHALER inhalers</description>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indacaterol</intervention_name>
    <description>Indacaterol inhalation capsules 150 mcg per dose will be supplied by GSK along with BREEZHALER inhalers manufactured by Novartis</description>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indacaterol matching placebo</intervention_name>
    <description>Indacaterol matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with BREEZHALER inhalers manufactured by Novartis</description>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Albuterol/salbutamol Metered Dose Inhaler (MDI)</intervention_name>
    <description>Albuterol/salbutamol MDI or nebules for as needed use will be issued throughout the study. Albuterol/salbutamol will be sourced from local commercial stock. If not available locally, GSK will source centrally</description>
    <arm_group_label>Tiotropium + Indacaterol arm</arm_group_label>
    <arm_group_label>UMEC/VI arm</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type of subject: Outpatient&#xD;
&#xD;
          -  Informed Consent: A signed and dated written informed consent prior to study&#xD;
             participation.&#xD;
&#xD;
          -  Participants 40 years of age or older at Visit 1.&#xD;
&#xD;
          -  Gender: Male or female participants. A female is eligible to enter and participate in&#xD;
             the study if she is of: Non-child bearing potential (i.e., physiologically incapable&#xD;
             of becoming pregnant, including any female who is post-menopausal or surgically&#xD;
             sterile). Surgically sterile females are defined as those with a documented&#xD;
             hysterectomy and/or bilateral oophorectomy or tubal ligation. Post-menopausal females&#xD;
             are defined as being amenorrhoeic for greater than 1 year with an appropriate clinical&#xD;
             profile, e.g., age appropriate, &gt; 45 years, in the absence of hormone replacement&#xD;
             therapy.OR Child bearing potential, has a negative pregnancy test at screening, and&#xD;
             agrees to one of the following acceptable contraceptive methods used consistently and&#xD;
             correctly (i.e., in accordance with the approved product label and the instructions of&#xD;
             the physician for the duration of the study screening to follow-up contact):&#xD;
             Abstinence, Oral Contraceptive, either combined or progestogen alone, Injectable&#xD;
             progestogen, Implants of levonorgestrel, Estrogenic vaginal ring, Percutaneous&#xD;
             contraceptive patches, Intrauterine device (IUD) or intrauterine system (IUS) that&#xD;
             meets the Standard Operating Procedure (SOP) effectiveness criteria as stated in the&#xD;
             product label, Male partner sterilization (vasectomy with documentation of&#xD;
             azoospermia) prior to the female subject's entry into the study, and this male is the&#xD;
             sole partner for that subject. For this definition, &quot;documented&quot; refers to the outcome&#xD;
             of the investigator's/designee's medical examination of the subject or review of the&#xD;
             subject's medical history for study eligibility, as obtained via a verbal interview&#xD;
             with the subject or from the subject' s medical records. Double barrier method: condom&#xD;
             and an occlusive cap (diaphragm or cervical/vault caps) with a vaginal spermicidal&#xD;
             agent (foam/gel/film/cream/suppository)&#xD;
&#xD;
          -  Diagnosis: An established clinical history of COPD in accordance with the definition&#xD;
             by the American Thoracic Society/European Respiratory Society.&#xD;
&#xD;
          -  Smoking History: Current or former cigarette smokers with a history of cigarette&#xD;
             smoking of &gt;=10 pack-years. Former smokers are defined as those who have stopped&#xD;
             smoking for at least 6 months prior to Visit 1.&#xD;
&#xD;
          -  Severity of Disease: A pre and post-albuterol/salbutamol Forced Expiratory Volume in&#xD;
             One Second/ Forced Vital Capacity (FEV1/ FVC) ratio of &lt;0.70 and a pre and&#xD;
             post-albuterol/salbutamol FEV1 of &lt;=70% predicted normal value at Visit 1, calculated&#xD;
             using Quanjer reference equations.&#xD;
&#xD;
          -  Dyspnoea: A score of &gt;= 2 on the Modified Medical Research Council Dyspnoea Scale&#xD;
             (mMRC) at Visit 1.&#xD;
&#xD;
          -  QT interval corrected (QTc) Criteria: QTc &lt;450 milliseconds (msec) or QTc &lt;480 msec&#xD;
             for patients with bundle branch block The QTc is the QT interval corrected for heart&#xD;
             rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or&#xD;
             another method, machine or manual overread. For subject eligibility and withdrawal,&#xD;
             QTcF will be used. For purposes of data analysis, QTcF will be used as primary. The&#xD;
             QTc should be based on single or averaged QTc values of triplicate Electrocardiogram&#xD;
             (ECGs) obtained over a brief recording period.&#xD;
&#xD;
          -  French participants: In France, a subject will be eligible for inclusion in this study&#xD;
             only if either affiliated to or a beneficiary of a social security category.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant&#xD;
             during the study.&#xD;
&#xD;
          -  Asthma: A current diagnosis of asthma.&#xD;
&#xD;
          -  Other Respiratory Disorders: Known alpha-1 antitrypsin deficiency, active lung&#xD;
             infections (such as tuberculosis), and lung cancer are absolute exclusionary&#xD;
             conditions. A subject who, in the opinion of the investigator, has any other&#xD;
             significant respiratory conditions in addition to COPD should be excluded. Examples&#xD;
             may include clinically significant bronchiectasis, pulmonary hypertension,&#xD;
             sarcoidosis, or interstitial lung disease. Allergy rhinitis is not exclusionary.&#xD;
&#xD;
          -  Other Diseases/Abnormalities: Participants with historical or current evidence of&#xD;
             clinically significant cardiovascular, neurological, psychiatric, renal, hepatic,&#xD;
             immunological, endocrine (including uncontrolled diabetes or thyroid disease) or&#xD;
             hematological abnormalities that are uncontrolled and/or a previous history of cancer&#xD;
             in remission for &lt;5 years prior to Visit 1 (localized carcinoma of the skin that has&#xD;
             been resected for cure is not exclusionary). Significant is defined as any disease&#xD;
             that, in the opinion of the investigator, would put the safety of the subject at risk&#xD;
             through participation, or which would affect the efficacy or safety analysis if the&#xD;
             disease/condition exacerbated during the study.&#xD;
&#xD;
          -  Contraindications: A history of allergy or hypersensitivity to any&#xD;
             anticholinergic/muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or&#xD;
             magnesium stearate or a medical condition such as narrow-angle glaucoma, prostatic&#xD;
             hypertrophy or bladder neck obstruction that, in the opinion of the study physician,&#xD;
             contraindicates study participation or use of an inhaled anticholinergic or beta 2&#xD;
             agonist.&#xD;
&#xD;
          -  Hospitalisation: Hospitalisation for COPD or pneumonia within 12 weeks prior to Visit&#xD;
             1.&#xD;
&#xD;
          -  Lung Resection: Participants with lung volume reduction surgery within the 12 months&#xD;
             prior to Screening (Visit 1).&#xD;
&#xD;
          -  12-Lead ECG: An abnormal and significant ECG finding from the 12-lead ECG conducted at&#xD;
             Visit 1. Specific ECG findings that preclude subject eligibility will be listed in&#xD;
             protocol The study investigator will determine the medical significance of any ECG&#xD;
             abnormalities not listed.&#xD;
&#xD;
          -  Screening labs: Significantly abnormal finding from clinical chemistry or haematology&#xD;
             tests at Visit 1 as determined by the study investigator.&#xD;
&#xD;
          -  Medication Prior to Spirometry: Unable to withhold albuterol/salbutamol for the 4 hour&#xD;
             period required prior to spirometry testing at each study visit.&#xD;
&#xD;
          -  Medications prior to Screening: Use of the following medications according to the&#xD;
             following defined time intervals prior to Visit 1: Depot corticosteroids (12 weeks);&#xD;
             Oral or parenteral corticosteroids (6 weeks); Antibiotics (for lower respiratory tract&#xD;
             infection) (6 weeks); Cytochrome P450 3A4 strong inhibitors ( 6 weeks); Long Acting&#xD;
             Beta-Agonist (LABA)/ inhaled corticosteroids (ICS) combination products (e.g.&#xD;
             fluticasone/salmeterol, mometasone, furoate/formoterol fumarate,&#xD;
             budesonide/formoterol, fumarate), If LABA/ICS therapy is discontinued completely (30&#xD;
             days); If discontinuing LABA therapy and switching to ICS monotherapy (48 hours for&#xD;
             salmeterol or formoterol, 14 days for Olodaterol, Indacaterol or, Vilanterol); Use of&#xD;
             ICS at a dose &gt;1000 mcg/day of fluticasone propionate or equivalent (30 days);&#xD;
             Initiation or discontinuation of ICS use (30 days); Inhaled long acting beta2-agonists&#xD;
             (LABA): Salmeterol, Formoterol (48 hours), Olodaterol, Indacaterol and Vilanterol (14&#xD;
             days); Long acting muscarinic antagonists (LAMA) (Tiotropium, Aclidinium,&#xD;
             Glycopyrronium, Umeclidinium) (7 days); LABA/LAMA combination products (Whichever mono&#xD;
             component has the longest washout); Roflumilast (14 days); Oral beta-agonists-&#xD;
             Long-acting (48 hours), Short-acting(12 hours); Theophyllines (48 hours); Oral&#xD;
             leukotriene inhibitors (zafirlukast, montelukast, zileuton) (48 hours); Inhaled sodium&#xD;
             cromoglycate or nedocromil sodium (24 hours); Inhaled short acting beta2-agonists (4&#xD;
             hours); Inhaled short-acting anticholinergic (short acting muscarinic antagonist&#xD;
             [SAMA]) products eg ipratropium (4 hours); Inhaled short-acting&#xD;
             anticholinergic/short-acting beta2-agonist combination products (SAMA/Short Acting&#xD;
             beta2-agonists [SABA]) (4 hours); Any other investigational medication (30 days or&#xD;
             within 5 drug half-lives)&#xD;
&#xD;
          -  Oxygen: Use of Long Term Oxygen Therapy (LTOT).This is defined as oxygen therapy&#xD;
             prescribed for greater than 12 hours per day. As needed oxygen use (i.e. &lt;=12 hours&#xD;
             per day) is not exclusionary.&#xD;
&#xD;
          -  Nebulized Therapy: Regular use (prescribed for use every day, not for as-needed use)&#xD;
             of short-acting bronchodilators (e.g., albuterol/salbutamol) via nebulized therapy.&#xD;
&#xD;
          -  Pulmonary Rehabilitation Program: Participation in the acute phase of a pulmonary&#xD;
             rehabilitation program within 12 weeks prior to Visit 1. Participants who are in the&#xD;
             maintenance phase of a pulmonary rehabilitation program are not excluded.&#xD;
&#xD;
          -  Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2&#xD;
             years prior to Visit 1.&#xD;
&#xD;
          -  Affiliation with Investigator Site: Is an investigator, sub-investigator, study&#xD;
             coordinator, employee of a participating investigator or study site, or immediate&#xD;
             family member of the aforementioned that is involved in this study.&#xD;
&#xD;
          -  Inability to read: In the opinion of the investigator, any subject who is unable to&#xD;
             read and/or would not be able to complete a questionnaire.&#xD;
&#xD;
          -  Participants who are pre-screen or screen failures cannot be re-screened.&#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>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>San Miguel de Tucuman</city>
        <state>Tucumán</state>
        <zip>4000</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>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>M5500CCG</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>Puente Alto - Santiago</city>
        <state>Región Metro De Santiago</state>
        <zip>8207257</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santiago</city>
        <state>Región Metro De Santiago</state>
        <zip>7500692</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santiago</city>
        <state>Región Metro De Santiago</state>
        <zip>7510186</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santiago</city>
        <zip>7500698</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Haapsalu</city>
        <zip>90502</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10117</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tallinn</city>
        <zip>10138</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gières</city>
        <zip>38610</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nantes cedex 2</city>
        <zip>44277</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>Reims Cedex</city>
        <zip>51092</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Strasbourg cedex</city>
        <zip>67091</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tarbes Cedex 09</city>
        <zip>65013</zip>
        <country>France</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>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>Schwerin</city>
        <state>Mecklenburg-Vorpommern</state>
        <zip>19055</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Magdeburg</city>
        <state>Sachsen-Anhalt</state>
        <zip>39112</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>10787</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Berlin</city>
        <zip>12203</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>20354</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>Balassagyarmat</city>
        <zip>2660</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Budaörs</city>
        <zip>2040</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Debrecen</city>
        <zip>4032</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gödöllő</city>
        <zip>2100</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nyíregyháza</city>
        <zip>4400</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Pécs</city>
        <zip>7635</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Szeged</city>
        <zip>6722</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Szikszó</city>
        <zip>3800</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Piacenza</city>
        <state>Emilia-Romagna</state>
        <zip>29121</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>Mantova</city>
        <state>Lombardia</state>
        <zip>46100</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>Novara</city>
        <state>Piemonte</state>
        <zip>28100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lima 27</city>
        <state>Lima</state>
        <zip>Lima 27</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lima</city>
        <zip>Lima 14</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lima</city>
        <zip>Lima 18</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lima</city>
        <zip>Lima 1</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lima</city>
        <zip>Lima 32</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Elblag</city>
        <zip>82-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Krakow</city>
        <zip>31-024</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ostrow Wielkopolski</city>
        <zip>63-400</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Piekary Slaskie</city>
        <zip>41-940</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Slupsk</city>
        <zip>76-200</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Sopot</city>
        <zip>81-741</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>020125</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bucharest</city>
        <zip>050159</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cluj Napoca</city>
        <zip>400371</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Constanta</city>
        <zip>900002</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ramnicu Valcea</city>
        <zip>240564</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Timisoara</city>
        <zip>300310</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Timisoara</city>
        <zip>300465</zip>
        <country>Romania</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Arkhangelsk</city>
        <zip>153000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620039</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620149</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Irkutsk</city>
        <zip>664079</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kazan</city>
        <zip>420015</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>115 478</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>125284</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Omsk</city>
        <zip>644112</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Orenburg</city>
        <zip>460040</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Perm</city>
        <zip>614068</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint Petesburg</city>
        <zip>195030</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>194356</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>St. Petersburg</city>
        <zip>198216</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Stavropol</city>
        <zip>355017</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tomsk</city>
        <zip>634063</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ulyanovsk</city>
        <zip>432063</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bojnice</city>
        <zip>972 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Humenne</city>
        <zip>066 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Poprad</city>
        <zip>058 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Spisska Nova Ves</city>
        <zip>052 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Vrable</city>
        <zip>952 01</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>Estonia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Italy</country>
    <country>Peru</country>
    <country>Poland</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Slovakia</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>December 10, 2015</results_first_submitted>
  <results_first_submitted_qc>February 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 3, 2016</results_first_posted>
  <last_update_submitted>February 2, 2018</last_update_submitted>
  <last_update_submitted_qc>February 2, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>indacaterol</keyword>
  <keyword>efficacy</keyword>
  <keyword>FEV1</keyword>
  <keyword>ELLIPTA</keyword>
  <keyword>non inferiority</keyword>
  <keyword>vilanterol</keyword>
  <keyword>COPD</keyword>
  <keyword>safety</keyword>
  <keyword>tiotropium</keyword>
  <keyword>umeclidinium bromide</keyword>
  <keyword>GSK573719</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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>Albuterol</mesh_term>
    <mesh_term>Tiotropium Bromide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116961</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Eligible participants (par) completed a 5-7 day run-in period, and were randomized to blinded study medication for 12 weeks. Supplemental albuterol/salbutamol was provided to all par, to be used on an as-needed basis during run-in and up to Day 85.</recruitment_details>
      <pre_assignment_details>A total of 1190 par were screened; 967 par randomized and 961 par comprised the Intent-to-Treat (ITT) Population (Pop), comprised of all par randomized to treatment (trt) who received at least 1 dose of randomized study medication in the trt period.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Umeclidinium/Vilanterol 62.5/25 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg), BREEZHALER containing placebo, and HANDIHALER containing placebo. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
        </group>
        <group group_id="P2">
          <title>Indacaterol 150 µg + Tiotropium Bromide 18 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing placebo, BREEZHALER containing indacaterol 150 µg, and HANDIHALER containing tiotropium bromide 18 µg. The inhaler containing placebo was identical in appearance to its corresponding inhaler containing active 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="482"/>
                <participants group_id="P2" count="479"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="460"/>
                <participants group_id="P2" count="457"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Umeclidinium/Vilanterol 62.5/25 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg), BREEZHALER containing placebo, and HANDIHALER containing placebo. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
        </group>
        <group group_id="B2">
          <title>Indacaterol 150 µg + Tiotropium Bromide 18 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing placebo, BREEZHALER containing indacaterol 150 µg, and HANDIHALER containing tiotropium bromide 18 µg. The inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="482"/>
            <count group_id="B2" value="479"/>
            <count group_id="B3" value="961"/>
          </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="64.4" spread="7.75"/>
                    <measurement group_id="B2" value="64.0" spread="8.44"/>
                    <measurement group_id="B3" value="64.2" spread="8.10"/>
                  </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="127"/>
                    <measurement group_id="B2" value="138"/>
                    <measurement group_id="B3" value="265"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="355"/>
                    <measurement group_id="B2" value="341"/>
                    <measurement group_id="B3" value="696"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>American Indian or Alaska Native</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - Central/South Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - Japanese Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - Arabic/North African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White -White/Caucasian/European Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="453"/>
                    <measurement group_id="B2" value="449"/>
                    <measurement group_id="B3" value="902"/>
                  </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) on Treatment Day 85 (Visit 8)</title>
        <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.</description>
        <time_frame>Baseline (BL) and Day 85</time_frame>
        <population>Per Protocol (PP) Pop: all ITT Pop par who were not full protocol deviators considered to impact efficacy. Only par with data available at the specified time points (TP) were analyzed but all par without (w/o) missing covariate information and with &gt;= 1 post BL measurement were included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Umeclidinium/Vilanterol 62.5/25 µg</title>
            <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg), BREEZHALER containing placebo, and HANDIHALER containing placebo. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
          </group>
          <group group_id="O2">
            <title>Indacaterol 150 µg + Tiotropium Bromide 18 µg</title>
            <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing placebo, BREEZHALER containing indacaterol 150 µg, and HANDIHALER containing tiotropium bromide 18 µg. The inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Treatment Day 85 (Visit 8)</title>
          <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.</description>
          <population>Per Protocol (PP) Pop: all ITT Pop par who were not full protocol deviators considered to impact efficacy. Only par with data available at the specified time points (TP) were analyzed but all par without (w/o) missing covariate information and with &gt;= 1 post BL measurement were 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="392"/>
                <count group_id="O2" value="392"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.172" spread="0.0107"/>
                    <measurement group_id="O2" value="0.171" spread="0.0108"/>
                  </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>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Alternate hypothesis:the difference between the trt means (umeclidinium/vilanterol minus indacaterol + tiotropium bromide) would be &gt; -50 milliliters (mL). If the lower CI (2.5% 1-sided significance level) of the statistical test should fall above -50 mL, then umeclidinium/vilanterol may be deemed statistically non-inferior to indacaterol plus tiotropium. If the lower CI (2.5% 1-sided significance) of the statistical testing exceeded 0 then, statistical superiority would have been established.</non_inferiority_desc>
            <p_value>0.964</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>0.001</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.029</ci_lower_limit>
            <ci_upper_limit>0.030</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84</title>
        <description>BL FEV1 was the mean of the 2 assessments made 30 and 5 min PD on Day 1. WM FEV1 derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1 and 84 using the 0-6 hr post-dose FEV1 measurements collected on that day, which included PD FEV1 (taken 30 and 5 min prior to dosing on Day 1 and the 30 and 5 min reading prior to dosing on Day 84) and post-dose FEV1 measurements at 1, 3 and 6 hr post-dose.WM change from BL was the WM at at the visit minus the BL value. Analysis was performed using a RM model with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1) center group, day, day by BL and day by trt interaction, where day was nominal. Only par with data available at the specified TP were analyzed but all par w/o missing covariate information and with &gt;=1 post-BL measurement were included in the analysis.</description>
        <time_frame>Baseline and Day 84</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Umeclidinium/Vilanterol 62.5/25 µg</title>
            <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg), BREEZHALER containing placebo, and HANDIHALER containing placebo. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
          </group>
          <group group_id="O2">
            <title>Indacaterol 150 µg + Tiotropium Bromide 18 µg</title>
            <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing placebo, BREEZHALER containing indacaterol 150 µg, and HANDIHALER containing tiotropium bromide 18 µg. The inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84</title>
          <description>BL FEV1 was the mean of the 2 assessments made 30 and 5 min PD on Day 1. WM FEV1 derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1 and 84 using the 0-6 hr post-dose FEV1 measurements collected on that day, which included PD FEV1 (taken 30 and 5 min prior to dosing on Day 1 and the 30 and 5 min reading prior to dosing on Day 84) and post-dose FEV1 measurements at 1, 3 and 6 hr post-dose.WM change from BL was the WM at at the visit minus the BL value. Analysis was performed using a RM model with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1) center group, day, day by BL and day by trt interaction, where day was nominal. Only par with data available at the specified TP were analyzed but all par w/o missing covariate information and with &gt;=1 post-BL measurement were included in the analysis.</description>
          <population>ITT Population</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="455"/>
                <count group_id="O2" value="452"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.235" spread="0.0111"/>
                    <measurement group_id="O2" value="0.258" spread="0.0111"/>
                  </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>Superiority or Other</non_inferiority_type>
            <p_value>0.145</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Least Squares Mean Difference</param_type>
            <param_value>-0.023</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.054</ci_lower_limit>
            <ci_upper_limit>0.008</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected over a period of a maximum of 96 days starting from Day 1 of treatment until the follow-up contact.</time_frame>
      <desc>On-treatment SAEs and non-serious AEs were reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.</desc>
      <group_list>
        <group group_id="E1">
          <title>Umeclidinium/Vilanterol 62.5/25 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing umeclidinium/vilanterol inhalation powder 62.5/25 micrograms (µg), BREEZHALER containing placebo, and HANDIHALER containing placebo. Each inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
        </group>
        <group group_id="E2">
          <title>Indacaterol 150 µg + Tiotropium Bromide 18 µg</title>
          <description>Participants self-administered one dose each morning from each of the following three inhalers for 12 weeks: ELLIPTA dry powder inhaler containing placebo, BREEZHALER containing indacaterol 150 µg, and HANDIHALER containing tiotropium bromide 18 µg. The inhaler containing placebo was identical in appearance to its corresponding inhaler containing active study medication.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (version 18)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="21" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title vocab="Angina pectoris">Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Atrioventricular block</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Myocardial ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Ventricular fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Crohn's disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Alcohol poisoning</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Concussion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Lower limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Spinal compression fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Brain neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Laryngeal cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of lung</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of the oral cavity</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cerebrovascular accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Circulatory collapse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Peripheral artery thrombosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="479"/>
              </event>
              <event>
                <sub_title>Peripheral ischaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA (version 18)</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="76" subjects_at_risk="482"/>
                <counts group_id="E2" subjects_affected="65" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" events="34" subjects_affected="32" subjects_at_risk="482"/>
                <counts group_id="E2" events="31" subjects_affected="27" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="56" subjects_affected="36" subjects_at_risk="482"/>
                <counts group_id="E2" events="60" subjects_affected="28" subjects_at_risk="479"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="18" subjects_affected="16" subjects_at_risk="482"/>
                <counts group_id="E2" events="18" subjects_affected="17" subjects_at_risk="479"/>
              </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>
    </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/NCT02257385
org study id: 116961
nct id: NCT02257385
lead sponsor: 
has dmc: No
This is a Phase IIIb multicentre, randomised, blinded, triple dummy, parallel group study to
      evaluate the efficacy and safety of UMEC/VI inhalation powder (62.5/25 microgram [mcg] Once
      daily [QD]) when administered via ELLIPTA® Dry Powder Inhaler (DPI) compared to indacaterol
      plus tiotropium (150 mcg/18 mcg respectively QD) administered via individual inhalers over a
      treatment period of 12 weeks in participants with moderate to very severe Chronic Obstructive
      Pulmonary Disease (COPD). The purpose of this study is to demonstrate that UMEC/VI (delivered
      via ELLIPTA DPI), when used in symptomatic moderate to very severe COPD participants, is
      non-inferior to the combination of indacaterol (delivered via BREEZHALER® inhaler) plus
      tiotropium (delivered via HANDIHALER® inhaler) on measures of trough forced expiratory volume
      in one second (FEV1) after 12 weeks of treatment. Participants who met the eligibility
      criteria at screening (Visit 1) will complete a 5 to 7 day run in period prior to
      randomisation at Visit 2. Clinic visits will follow at day 2, week 2, week 4, week 8 and week
      12 of treatment, plus week 12 + 1 day (Visits 3 to 8). The total duration of study
      participation will be approximately 14 weeks. ELLIPTA is a registered trademark of the GSK
      group of companies. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH
      & Co. KG. BREEZHALER is a registered trademark of Novartis AG.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Treatment Day 85 (Visit 8)
time frame: Baseline (BL) and Day 85
description: FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in 1 second. BL was the mean of the 2 assessments made 30 and 5 minutes (min) pre-dose (PD) on Day 1. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after dosing on Day 84 (at Week 12 + 1 day). Analysis was performed using mixed model repeated measures (RM) with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1), center group, day, day by BL interaction and day by trt interaction, where day was nominal.
measure: Change From Baseline in Weighted Mean (WM) FEV1 Over 0-6 Hour Post-dose at Day 84
time frame: Baseline and Day 84
description: BL FEV1 was the mean of the 2 assessments made 30 and 5 min PD on Day 1. WM FEV1 derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1 and 84 using the 0-6 hr post-dose FEV1 measurements collected on that day, which included PD FEV1 (taken 30 and 5 min prior to dosing on Day 1 and the 30 and 5 min reading prior to dosing on Day 84) and post-dose FEV1 measurements at 1, 3 and 6 hr post-dose.WM change from BL was the WM at at the visit minus the BL value. Analysis was performed using a RM model with covariates of trt, BL FEV1 (mean of values measured at 30 and 5 min PD on Day 1) center group, day, day by BL and day by trt interaction, where day was nominal. Only par with data available at the specified TP were analyzed but all par w/o missing covariate information and with >=1 post-BL measurement were included in the analysis.
arm group label: UMEC/VI arm
arm group type: Experimental
description: Participants will be instructed to self-administer one dose each morning of UMEC/VI Inhalation Powder 62.5/25 mcg once daily via ELLIPTA DPI, placebo once daily via HANDIHALER inhaler and placebo once daily via BREEZHALER inhaler
arm group label: Tiotropium + Indacaterol arm
arm group type: Placebo Comparator
description: Participants will be instructed to self-administer one dose each morning of Tiotropium bromide 18 mcg once daily via HANDIHALER inhaler, Indacaterol 150 mcg once daily via BREEZHALER inhaler and placebo once daily via ELLIPTA DPI
intervention type: Drug
intervention name: UMEC/VI
description: ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains Umeclidinium bromide (unit dose strengths 62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate 0.6% weight/weight (w/w) of total drug product and second strip contains Vilanterol (unit dose strengths 25 mcg per blister) blended with lactose monohydrate and magnesium stearate 1.0% w/w of total drug product
arm group label: UMEC/VI arm
intervention type: Drug
intervention name: UMEC/VI matching placebo
description: ELLIPTA DPI will be supplied with 30 doses (2 strips with 30 blisters per strip) where first strip contains lactose monohydrate and magnesium stearate 0.6% w/w of total drug product and second strip contains lactose monohydrate and magnesium stearate 1.0% w/w of total drug product
arm group label: UMEC/VI arm
intervention type: Drug
intervention name: Tiotropium
description: Tiotropium (as bromide monohydrate) inhalation capsules 18 mcg per dose will be supplied along with HANDIHALER inhalers manufactured by Boehringer Ingelheim
arm group label: Tiotropium + Indacaterol arm
intervention type: Drug
intervention name: Tiotropium matching placebo
description: Tiotropium matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with HANDIHALER inhalers
arm group label: Tiotropium + Indacaterol arm
intervention type: Drug
intervention name: Indacaterol
description: Indacaterol inhalation capsules 150 mcg per dose will be supplied by GSK along with BREEZHALER inhalers manufactured by Novartis
arm group label: Tiotropium + Indacaterol arm
intervention type: Drug
intervention name: Indacaterol matching placebo
description: Indacaterol matching placebo capsules manufactured by GSK, will contain lactose and will be supplied along with BREEZHALER inhalers manufactured by Novartis
arm group label: Tiotropium + Indacaterol arm
intervention type: Drug
intervention name: Albuterol/salbutamol Metered Dose Inhaler (MDI)
description: Albuterol/salbutamol MDI or nebules for as needed use will be issued throughout the study. Albuterol/salbutamol will be sourced from local commercial stock. If not available locally, GSK will source centrally
arm group label: Tiotropium + Indacaterol arm
arm group label: UMEC/VI arm
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: Chile
country: Estonia
country: France
country: Germany
country: Hungary
country: Italy
country: Peru
country: Poland
country: Romania
country: Russian Federation
country: Slovakia
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Albuterol
mesh term: Tiotropium Bromide
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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