<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/NCT02236611</url>
  </required_header>
  <id_info>
    <org_study_id>201315</org_study_id>
    <nct_id>NCT02236611</nct_id>
  </id_info>
  <brief_title>A 12-week Study to Evaluate the Efficacy and Safety of Umeclidinium 62.5 Microgram (mcg) Compared With Glycopyrronium 44 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>A Randomized, Parallel-group, Open-label Study to Evaluate the Efficacy and Safety of Umeclidinium (UMEC) 62.5 mcg Compared With Glycopyrronium 44 mcg in Subjects With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 12-week, multicentre, randomized, open-label, 2-arm, parallel-group study designed&#xD;
      to compare the efficacy and safety of umeclidinium inhalation powder (62.5 mcg once daily&#xD;
      [QD]) administered via a novel Dry Powder Inhaler (nDPI) with glycopyrronium (44 mcg QD)&#xD;
      administered via a Breezhaler® inhaler in subjects with COPD over 12 weeks of treatment. At&#xD;
      the end of the run-in period, eligible subjects will be randomized in a 1:1 ratio to receive&#xD;
      umeclidinium 62.5 mcg administered via nDPI or glycopyrronium 44 mcg administered via&#xD;
      BREEZHALER inhaler. There will be up to 8 clinic visits conducted on an outpatient basis at&#xD;
      Pre-Screening (Visit 0), Screening (Visit 1), Randomization at Day 1 (Visit 2), and after&#xD;
      Randomization at Day 2 (Visit 3), Day 28 (Visit 4), Day 56 (Visit 5), Day 84 (Visit 6) and&#xD;
      Day 85 (Visit 7). The total duration of subject participation in the study will be&#xD;
      approximately 15 weeks. The primary endpoint of the study is clinic visit trough FEV1 (forced&#xD;
      expiratory volume in one second) on treatment Day 85. All subjects will have spirometry&#xD;
      performed at clinic Visits 1 though 7. Trough spirometry will be obtained 23 and 24 hours&#xD;
      after the previous day's dose of open-label study medication at Visits 3 to 7.&#xD;
&#xD;
      BREEZHALER is a registered trademark of Novartis AG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2014</start_date>
  <completion_date type="Actual">June 2, 2015</completion_date>
  <primary_completion_date type="Actual">June 2, 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Trough FEV1 on Day 85</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 one second. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1036</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Umeclidinium 62.5 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized subjects will receive umeclidinium inhalation powder 62.5 mcg, once daily over a period of 12 weeks via a nDPI. Subjects will be instructed to take one dose each morning.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glycopyrronium 44 mcg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomized subjects will receive glycopyrronium 44 mcg, once daily over a period of 12 weeks via a BREEZHALER inhaler. Subjects will be instructed to take one dose each morning.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Umeclidinium</intervention_name>
    <description>Umeclidinium 62.5 mcg will be available as dry inhalation powder to be taken using a nDPI</description>
    <arm_group_label>Umeclidinium 62.5 mcg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glycopyrronium</intervention_name>
    <description>Glycopyrronium bromide will be available as inhalation capsules, 44 mcg per capsule, taken using BREEZHALER inhalers</description>
    <arm_group_label>Glycopyrronium 44 mcg</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;
          -  Age: subjects 40 years of age or older at Visit 1.&#xD;
&#xD;
          -  Gender: male and female subjects are eligible to participate in the study. A female is&#xD;
             eligible to enter and participate in the study if she is of: Non-child bearing&#xD;
             potential i.e., physiologically incapable of becoming pregnant, including any female&#xD;
             who is post-menopausal or surgically sterile. Surgically sterile females are defined&#xD;
             as those with a documented hysterectomy and/or bilateral oophorectomy or tubal&#xD;
             ligation. Post-menopausal females are defined as being amenorrhoeic for greater than 1&#xD;
             year with an appropriate clinical profile, eg, age appropriate, &gt; 45 years, in the&#xD;
             absence of hormone replacement therapy OR child bearing potential, has a negative&#xD;
             pregnancy test at screening, and agrees to one of the acceptable contraceptive methods&#xD;
             used consistently and correctly i.e., in accordance with the approved product label&#xD;
             and the instructions of the physician for the duration of the study - screening to&#xD;
             follow-up contact.&#xD;
&#xD;
          -  Diagnosis: an established clinical history of COPD in accordance with the definition&#xD;
             by the American Thoracic Society/European Respiratory Society (ERS)&#xD;
&#xD;
          -  Smoking history: current or former cigarette smokers with a history of cigarette&#xD;
             smoking of &gt;= 10 pack-years [number of pack years = (number of cigarettes per day /&#xD;
             20) x number of years smoked (eg. 20 cigarettes per day for 10 years, or 10 cigarettes&#xD;
             per day for 20 years both equal 10 pack-years)]. Former smokers are defined as those&#xD;
             who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use&#xD;
             cannot be used to calculate pack-year history&#xD;
&#xD;
          -  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&#xD;
             post-albuterol/salbutamol FEV1 of &gt;=30% and =&lt;70% of predicted normal values at Visit&#xD;
             1. Predicted values will be based upon the ERS Global Lung Function Initiative&#xD;
&#xD;
          -  Dyspnea: A score of &gt;=2 on the modified medical research council dyspnea scale (mMRC)&#xD;
             at Visit 1&#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.&#xD;
&#xD;
          -  Other diseases/abnormalities: any subject who is considered unlikely to survive the&#xD;
             duration of the study period or has any rapidly progressing disease or immediate&#xD;
             life-threatening illness (e.g. cancer). In addition, any subject who has any condition&#xD;
             (e.g. neurological condition) that is likely to affect respiratory function should not&#xD;
             be included in the study.&#xD;
&#xD;
          -  Severe hepatic impairment: patients with severe hepatic impairment (Child-Pugh class&#xD;
             C) should be excluded unless, in the opinion of the investigator, the benefit is&#xD;
             likely to outweigh the risk.&#xD;
&#xD;
          -  Severe renal impairment: patients with severe renal impairment (e.g., end-stage renal&#xD;
             disease requiring dialysis) should be excluded, unless in the opinion of the&#xD;
             investigator, the benefit is likely to outweigh the risk.&#xD;
&#xD;
          -  Unstable or life threatening cardiac disease: long-acting muscarinic antagonists&#xD;
             (LAMA) should be used with caution in subjects with severe cardiovascular disease. In&#xD;
             the opinion of the investigator, use should only be considered if the benefit is&#xD;
             likely to outweigh the risk in conditions such as: Myocardial infarction or unstable&#xD;
             angina in the last 6 months, Unstable or life threatening cardiac arrhythmia requiring&#xD;
             intervention in the last 3 months, New York Heart Association (NYHA) Class IV heart&#xD;
             failure&#xD;
&#xD;
          -  Contraindications: Any history of allergy or hypersensitivity to any anticholinergic/&#xD;
             muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium&#xD;
             stearate.&#xD;
&#xD;
          -  Antimuscarinic effects: Subjects with medical conditions such as narrow-angle&#xD;
             glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction should&#xD;
             only be included if, in the opinion of the study physician, the benefit outweighs the&#xD;
             risk.&#xD;
&#xD;
          -  Hospitalization: hospitalization for COPD or pneumonia within 12 weeks prior to Visit&#xD;
             1.&#xD;
&#xD;
          -  Lung resection: lung volume reduction surgery within the 12 months prior to Visit 1.&#xD;
&#xD;
          -  12-Lead electrocardiogram (ECG): Investigators will be provided with ECG reviews&#xD;
             conducted by a centralized independent cardiologist to assist in evaluation of subject&#xD;
             eligibility. The Investigator will determine the clinical significance of each&#xD;
             abnormal ECG finding in relation to the subject's medical history and exclude subjects&#xD;
             who would be at undue risk by participating in the trial. Subjects with the following&#xD;
             abnormalities are excluded from participation in the study: Atrial fibrillation with&#xD;
             rapid ventricular rate &gt;120 beats per minute; sustained or nonsustained ventricular&#xD;
             tachycardia; second degree heart block Mobitz type II or third degree heart block&#xD;
             (unless pacemaker or defibrillator had been inserted)&#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;
             systemic, oral or parenteral corticosteroids 6 weeks, antibiotics (for lower&#xD;
             respiratory tract infection) 6 weeks, inhaled long acting beta2 agonists/ inhaled&#xD;
             corticosteroid (LABA/ICS) combination products if LABA/ICS therapy is discontinued&#xD;
             completely 30 days; LABA/ICS combination products only If discontinuing ICS/ LABA&#xD;
             therapy and switching to ICS monotherapy 48 hours for the salmeterol or formoterol&#xD;
             component 14 days for the vilanterol component (note: the dose of ICS must be a dose&#xD;
             of fluticasone propionate (FP) or equivalent but not to exceed 1000 mcg/day), use of&#xD;
             ICS at a dose &gt;1000 microgram (mcg)/day of FP or equivalent 30 days (note: use of ICS&#xD;
             is permitted provided the dose does not exceed 1000 mcg of FP or equivalent; ICS use&#xD;
             not to be initiated or discontinued within 30 days prior to Visit 1, except for&#xD;
             subjects on LABA/ICS therapy who may discontinue the ICS/LABA product as indicated in&#xD;
             the table above and switch to ICS monotherapy); initiation or discontinuation of ICS&#xD;
             use 30 days (note: use of ICS is permitted provided the dose does not exceed 1000 mcg&#xD;
             of FP or equivalent; ICS use not to be initiated or discontinued within 30 days prior&#xD;
             to Visit 1, except for subjects on LABA/ICS therapy who may discontinue the ICS/LABA&#xD;
             product as indicated in the table above and switch to ICS monotherapy);&#xD;
             phosphodiesterase 4 (PDE4) Inhibitor (roflumilast) 14 days; LABA: salmeterol and&#xD;
             formoterol 48 hours; olodaterol, indacaterol, and vilanterol 14 days; LAMA:&#xD;
             tiotropium, aclidinium, glycopyrronium, umeclidinium 7 days; LAMA/LABA combination&#xD;
             products if LAMA/LABA therapy is discontinued completely then apply whichever mono&#xD;
             component has the longest washout; theophyllines 48 hours; Oral beta2-agonists:&#xD;
             long-acting 48 hours, short-acting 12 hours; inhaled short acting beta2-agonists 4&#xD;
             hours (note: use of study provided albuterol/salbutamol is permitted during the study,&#xD;
             except in the 4-hour period prior to spirometry testing); inhaled short-acting&#xD;
             anticholinergics 4 hours; inhaled short-acting anticholinergic/short-acting&#xD;
             beta2-agonist combination products 4 hours; any other investigational medication 30&#xD;
             days or within 5 drug half-lives (whichever is longer).&#xD;
&#xD;
          -  Oxygen: use of long-term oxygen therapy (LTOT) described as oxygen therapy prescribed&#xD;
             for greater than 12 hours a day. As-needed oxygen use (i.e. =&lt;12 hours per day) is not&#xD;
             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 4 weeks prior to Visit 1. Subjects 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;
      </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>Paraná</city>
        <state>Buenos Aires</state>
        <zip>E3100BHK</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Concepcion del Uruguay</city>
        <state>Entre Ríos</state>
        <zip>3260</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Rafael</city>
        <state>Mendoza</state>
        <zip>5600</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rosario</city>
        <state>Santa Fe</state>
        <zip>S2000JKR</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 Tucuman</city>
        <zip>T4000IFL</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>Concepción</city>
        <state>Región Del Biobio</state>
        <zip>4070038</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Talca</city>
        <state>Región Del Maule</state>
        <zip>3465584</zip>
        <country>Chile</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>7500710</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>
        <state>Región Metro De Santiago</state>
        <zip>8242238</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>Santiago</city>
        <zip>8380453</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jindrichuv Hradec</city>
        <zip>377 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kralupy nad Vltavou</city>
        <zip>278 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lovosice</city>
        <zip>410 02</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ostrava - Poruba</city>
        <zip>70868</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rudna U Prahy</city>
        <zip>252 19</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Trebic</city>
        <zip>674 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Varnsdorf</city>
        <zip>407 47</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bamberg</city>
        <state>Bayern</state>
        <zip>96049</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Muenchen</city>
        <state>Bayern</state>
        <zip>80539</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>Brinkum/Stuhr</city>
        <state>Niedersachsen</state>
        <zip>28816</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30167</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hannover</city>
        <state>Niedersachsen</state>
        <zip>30173</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Dueren</city>
        <state>Nordrhein-Westfalen</state>
        <zip>52349</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Essen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45359</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Gelsenkirchen</city>
        <state>Nordrhein-Westfalen</state>
        <zip>45879</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Koblenz</city>
        <state>Rheinland-Pfalz</state>
        <zip>56068</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04103</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04275</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <state>Sachsen</state>
        <zip>04357</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Luebeck</city>
        <state>Schleswig-Holstein</state>
        <zip>23552</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>Budapest</city>
        <zip>1085</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>Debrecen</city>
        <zip>4043</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kapuvár</city>
        <zip>9330</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nagykanizsa</city>
        <zip>8800</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Törökbálint</city>
        <zip>2045</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hakadal</city>
        <zip>1487</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hamar</city>
        <zip>2317</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hønefoss</city>
        <zip>N-3515</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kolbjørnsvik</city>
        <zip>4816</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kongsvinger</city>
        <zip>N-2200</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Løvenstad</city>
        <zip>2006</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ålesund</city>
        <zip>6017</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Brasov</city>
        <zip>500283</zip>
        <country>Romania</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>Cluj Napoca</city>
        <zip>400371</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>Iasi</city>
        <zip>700115</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>Suceava</city>
        <zip>720284</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>Barnaul</city>
        <zip>656024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barnaul</city>
        <zip>656038</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454076</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454091</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chelyabinsk</city>
        <zip>454106</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chita</city>
        <zip>672000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ekaterinburg</city>
        <zip>620109</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Irkutsk</city>
        <zip>664005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ivanovo</city>
        <zip>153005</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kazan</city>
        <zip>420012</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kemerovo</city>
        <zip>650000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>105 077</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>119620</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Moscow</city>
        <zip>125315</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nizhniy Novgorod</city>
        <zip>603126</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Novosibirsk</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Perm</city>
        <zip>614097</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Ryazan,</city>
        <zip>390026</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>Saint-Petersburg</city>
        <zip>194044</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>194354</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>194356</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>195271</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>Laredo</city>
        <state>Cantabria</state>
        <zip>39770</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08017</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08023</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08028</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fuenlabrada / Madrid</city>
        <zip>28943</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>La Roca Del Valles (Barcelona)</city>
        <zip>08430</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Peralada( Girona)</city>
        <zip>17491</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Göteborg</city>
        <zip>SE-413 45</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Göteborg</city>
        <zip>SE-413 90</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-111 57</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Stockholm</city>
        <zip>SE-113 61</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Chile</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Norway</country>
    <country>Romania</country>
    <country>Russian Federation</country>
    <country>Spain</country>
    <country>Sweden</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_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>April 2018</verification_date>
  <study_first_submitted>September 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <results_first_submitted>January 18, 2016</results_first_submitted>
  <results_first_submitted_qc>January 18, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">February 15, 2016</results_first_posted>
  <last_update_submitted>April 30, 2018</last_update_submitted>
  <last_update_submitted_qc>April 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 2, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COPD</keyword>
  <keyword>inhaler ease of use</keyword>
  <keyword>glycopyrronium</keyword>
  <keyword>umeclidinium</keyword>
  <keyword>novel dry powder inhaler</keyword>
  <keyword>long-acting muscarinic antagonist</keyword>
  <keyword>inhaler errors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Glycopyrrolate</mesh_term>
  </intervention_browse>
  <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>201315</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>201315</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>201315</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_doc>
      <doc_id>201315</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>201315</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>201315</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>201315</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_docs>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 1290 par. were screened; 1037 par. were randomized and 1034 were in the ITT population which comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Two par. were randomized in error and one par. was randomized, but did not take any study medication.</recruitment_details>
      <pre_assignment_details>Participants, with clinical history of chronic obstructive pulmonary disease, who meet the eligibility criteria at screening were enrolled in a 7 to 14 day run-in period. Participant meeting continuation criteria, during run-in period, were randomized (1:1) to receive umeclidinium or glycopyrronium.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>UMEC 62.5 mcg QD</title>
          <description>Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study.</description>
        </group>
        <group group_id="P2">
          <title>GLYCO 44 mcg QD</title>
          <description>Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="516"/>
                <participants group_id="P2" count="518"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="490"/>
                <participants group_id="P2" count="484"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
                <participants group_id="P2" count="34"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <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="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol deviation</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrew consent</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <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>UMEC 62.5 mcg QD</title>
          <description>Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study.</description>
        </group>
        <group group_id="B2">
          <title>GLYCO 44 mcg QD</title>
          <description>Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.</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="516"/>
            <count group_id="B2" value="518"/>
            <count group_id="B3" value="1034"/>
          </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="64.1" spread="8.35"/>
                    <measurement group_id="B2" value="64.0" spread="8.26"/>
                    <measurement group_id="B3" value="64.1" spread="8.30"/>
                  </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="161"/>
                    <measurement group_id="B2" value="168"/>
                    <measurement group_id="B3" value="329"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="355"/>
                    <measurement group_id="B2" value="350"/>
                    <measurement group_id="B3" value="705"/>
                  </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>Central/South Asian Heritage (HRTG)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Japanese/East Asian Heritage/South East Asian HRTG</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</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="513"/>
                    <measurement group_id="B2" value="517"/>
                    <measurement group_id="B3" value="1030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Trough FEV1 on Day 85</title>
        <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.</description>
        <time_frame>Baseline (BL) and Day 85</time_frame>
        <population>Per Protocol(PP) Population(pop): Participants(par) in the Intent-To-Treat pop who did not have a full protocol deviation considered to impact efficacy. Par represent those with data available at time point presented; however, all par. in the PP pop. without missing covariate information and &gt;=1 post BL measurement are included in analysis</population>
        <group_list>
          <group group_id="O1">
            <title>UMEC 62.5 mcg QD</title>
            <description>Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study.</description>
          </group>
          <group group_id="O2">
            <title>GLYCO 44 mcg QD</title>
            <description>Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Trough FEV1 on Day 85</title>
          <description>FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.</description>
          <population>Per Protocol(PP) Population(pop): Participants(par) in the Intent-To-Treat pop who did not have a full protocol deviation considered to impact efficacy. Par represent those with data available at time point presented; however, all par. in the PP pop. without missing covariate information and &gt;=1 post BL measurement are included in analysis</population>
          <units>Liter</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="431"/>
                <count group_id="O2" value="425"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.123" spread="0.0105"/>
                    <measurement group_id="O2" value="0.099" spread="0.0105"/>
                  </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 minus glycopyrronium) 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 may be deemed statistically non-inferior to glycopyrronium. If the lower CI (2.5% 1-sided significance) of the statistical testing exceeded 0 then, umeclidinium may be deemed statistically superior to glycopyrronium.</non_inferiority_desc>
            <p_value>0.100</p_value>
            <method>Mixed Models Analysis</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.024</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.005</ci_lower_limit>
            <ci_upper_limit>0.054</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>On-treatment(trt) non-serious adverse events(AEs) and serious AEs are events occurring while par were on trt or events with an onset during follow-up period(up to 13 weeks).</time_frame>
      <desc>On-treatment SAEs and non-serious AEs were reported for the Intent-To Treat Population comprised 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>UMEC 62.5 mcg QD</title>
          <description>Participants received Umeclidinium (UMEC) inhalation powder 62.5 microgram (mcg) once-daily (QD) in morning via a novel dry powder inhaler (nDPI) for 12 weeks. Participants also received albuterol/salbutamol via metered-dose-inhaler (MDI) or nebules as needed throughout the study.</description>
        </group>
        <group group_id="E2">
          <title>GLYCO 44 mcg QD</title>
          <description>Participants received glycopyrronium bromide (GLYCO) inhalation capsules 44 mcg QD in morning via an alternative dry powder inhaler (DPI) for 12 weeks. Participants also received albuterol/salbutamol via MDI or nebules as needed throughout the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Acute coronary syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Cardiac failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Mouth ulceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Rectal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden cardiac death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </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="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ankle fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Femoral neck fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Hip fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Foot deformity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Laryngeal cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Neoplasm malignant</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </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="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="518"/>
              </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="7" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="518"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>3</frequency_threshold>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="77" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="80" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="39" subjects_at_risk="518"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="516"/>
                <counts group_id="E2" subjects_affected="51" subjects_at_risk="518"/>
              </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/NCT02236611
org study id: 201315
nct id: NCT02236611
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a 12-week, multicentre, randomized, open-label, 2-arm, parallel-group study designed
      to compare the efficacy and safety of umeclidinium inhalation powder (62.5 mcg once daily
      [QD]) administered via a novel Dry Powder Inhaler (nDPI) with glycopyrronium (44 mcg QD)
      administered via a Breezhaler® inhaler in subjects with COPD over 12 weeks of treatment. At
      the end of the run-in period, eligible subjects will be randomized in a 1:1 ratio to receive
      umeclidinium 62.5 mcg administered via nDPI or glycopyrronium 44 mcg administered via
      BREEZHALER inhaler. There will be up to 8 clinic visits conducted on an outpatient basis at
      Pre-Screening (Visit 0), Screening (Visit 1), Randomization at Day 1 (Visit 2), and after
      Randomization at Day 2 (Visit 3), Day 28 (Visit 4), Day 56 (Visit 5), Day 84 (Visit 6) and
      Day 85 (Visit 7). The total duration of subject participation in the study will be
      approximately 15 weeks. The primary endpoint of the study is clinic visit trough FEV1 (forced
      expiratory volume in one second) on treatment Day 85. All subjects will have spirometry
      performed at clinic Visits 1 though 7. Trough spirometry will be obtained 23 and 24 hours
      after the previous day's dose of open-label study medication at Visits 3 to 7.

      BREEZHALER is a registered trademark of Novartis AG.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Baseline in Trough FEV1 on Day 85
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 one second. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84 and 85. Baseline trough FEV1 is the mean of the two assessments made -30 and -5 minutes (min) pre-dose on Day 1. Change from baseline was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis performed using a repeated measures model with covariates of treatment, baseline FEV1, centre group, 24 hour subset flag, Day, Day by baseline and Day by treatment interactions. The least squares mean changes are presented here.
arm group label: Umeclidinium 62.5 mcg
arm group type: Experimental
description: Randomized subjects will receive umeclidinium inhalation powder 62.5 mcg, once daily over a period of 12 weeks via a nDPI. Subjects will be instructed to take one dose each morning.
arm group label: Glycopyrronium 44 mcg
arm group type: Experimental
description: Randomized subjects will receive glycopyrronium 44 mcg, once daily over a period of 12 weeks via a BREEZHALER inhaler. Subjects will be instructed to take one dose each morning.
intervention type: Drug
intervention name: Umeclidinium
description: Umeclidinium 62.5 mcg will be available as dry inhalation powder to be taken using a nDPI
arm group label: Umeclidinium 62.5 mcg
intervention type: Drug
intervention name: Glycopyrronium
description: Glycopyrronium bromide will be available as inhalation capsules, 44 mcg per capsule, taken using BREEZHALER inhalers
arm group label: Glycopyrronium 44 mcg
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: Czechia
country: Germany
country: Hungary
country: Norway
country: Romania
country: Russian Federation
country: Spain
country: Sweden
country: Czech Republic
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: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Glycopyrrolate
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.
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 