A 24-week Study to Compare Umeclidinium/Vilanterol (UMEC/VI), UMEC and Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

A 24-week Treatment, Multi-center, Randomized, Double-blind, Double-dummy, Parallel Group Study to Compare Umeclidinium/Vilanterol, Umeclidinium, and Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

COPD is characterized by an airflow limitation, which is not fully reversible, usually progressive and accompanied by chronic cough, sputum production and dyspnea, which can be a major cause of disability and anxiety associated with the disease. In addition, COPD is associated with poor health-related quality of life (HRQoL). Pharmacologic therapy is used to improve lung function, reduce symptoms, reduce the frequency and severity of exacerbations, and also to improve health status and exercise tolerance.

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

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

ELLIPTA and DISKUS are trademarks of GSK group of companies.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: UMEC/VI 62.5/25 mcg via ELLIPTA; Drug: Placebo via DISKUS; Drug: UMEC 62.5 mcg via ELLIPTA; Drug: Salmeterol 50 mcg via DISKUS; Drug: Placebo via ELLIPTA

• Study Type: Interventional
• Enrollment (Actual): 2696
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424BSF
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1120AAC
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1425BEN
    • GSK Investigational Site
  • Capital Federal, Argentina, C1440BRR
    • GSK Investigational Site
  • Ciudad Autonoma de Buenis Aires, Argentina, C1015ABR
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1128AAF
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
    • GSK Investigational Site
  • Mendoza, Argentina, M5500CCG
    • GSK Investigational Site
  • Mendoza, Argentina, 5500
    • GSK Investigational Site
  • Mendoza, Argentina, 5501
    • GSK Investigational Site
  • Monte Grande, Argentina, 1842
    • GSK Investigational Site
  • San Miguel de Tucumán, Argentina, 4000
    • GSK Investigational Site
  • Santa Fe, Argentina, 3000
    • GSK Investigational Site
  • Santa Rosa, Argentina, 6300
    • GSK Investigational Site
  • Tucumán, Argentina, T4000DGF
    • GSK Investigational Site
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1028AAP
      • GSK Investigational Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1414AIF
      • GSK Investigational Site
    • Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina, C1425AGC
      • GSK Investigational Site
    • Florida, Buenos Aires, Argentina, 1602
      • GSK Investigational Site
    • La Plata, Buenos Aires, Argentina
      • GSK Investigational Site
    • Lobos, Buenos Aires, Argentina, 7240
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • GSK Investigational Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • GSK Investigational Site
    • Paraná, Buenos Aires, Argentina, E3100BHK
      • GSK Investigational Site
    • Quilmes, Buenos Aires, Argentina, B1878FNR
      • GSK Investigational Site
    • Vicente Lopez, Buenos Aires, Argentina, B1602DOH
      • GSK Investigational Site
  • Córdova
    • Cordoba, Córdova, Argentina, X5003DCE
      • GSK Investigational Site
  • Entre Ríos
    • Concepcion del Uruguay, Entre Ríos, Argentina, 3260
      • GSK Investigational Site
  • Mendoza
    • San Rafael, Mendoza, Argentina, 5600
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, 2000
      • GSK Investigational Site
    • Rosario, Santa Fe, Argentina, S2002OJN
      • GSK Investigational Site
• Australia
  • New South Wales
    • Coffs Harbour, New South Wales, Australia, 2450
      • GSK Investigational Site
    • Darlinghurst, Sydney, New South Wales, Australia, 2010
      • GSK Investigational Site
    • Kanwal, New South Wales, Australia, 2259
      • GSK Investigational Site
    • Port Macquarie, New South Wales, Australia, 2444
      • GSK Investigational Site
    • Sydney, New South Wales, Australia, 2010
      • GSK Investigational Site
• Canada
  • Quebec, Canada, G1W 4R4
    • GSK Investigational Site
  • Quebec, Canada, G1V 4G5
    • GSK Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G1A7
      • GSK Investigational Site
  • Nova Scotia
    • Truro, Nova Scotia, Canada, B2N 1L2
      • GSK Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8L 5G8
      • GSK Investigational Site
    • London, Ontario, Canada, N5W 6A2
      • GSK Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M9V 4B4
      • GSK Investigational Site
    • Windsor, Ontario, Canada, N8X 1T3
      • GSK Investigational Site
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 6S8
      • GSK Investigational Site
    • Mirabel, Quebec, Canada, J7J 2K8
      • GSK Investigational Site
    • Montréal, Quebec, Canada, H1M 1B1
      • GSK Investigational Site
    • St. Charles-Borromee, Quebec, Canada, J6E 2B4
      • GSK Investigational Site
• France
  • Marseille cedex 03, France, 13331
    • GSK Investigational Site
  • Nice, France, 06000
    • GSK Investigational Site
  • Perpignan, France, 66000
    • GSK Investigational Site
  • Pessac cedex, France, 33604
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 10367
    • GSK Investigational Site
  • Berlin, Germany, 14059
    • GSK Investigational Site
  • Berlin, Germany, 13086
    • GSK Investigational Site
  • Berlin, Germany, 10117
    • GSK Investigational Site
  • Berlin, Germany, 10717
    • GSK Investigational Site
  • Berlin, Germany, 10119
    • GSK Investigational Site
  • Berlin, Germany, 10787
    • GSK Investigational Site
  • Berlin, Germany, 12627
    • GSK Investigational Site
  • Berlin, Germany, 10625
    • GSK Investigational Site
  • Berlin, Germany, 13156
    • GSK Investigational Site
  • Frankfurt, Germany, 60313
    • GSK Investigational Site
  • Hamburg, Germany, 22143
    • GSK Investigational Site
  • Hamburg, Germany, 20253
    • GSK Investigational Site
  • Hamburg, Germany, 22299
    • GSK Investigational Site
  • Leipzig, Germany, 04207
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Karlsruhe, Baden-Wuerttemberg, Germany, 76137
      • GSK Investigational Site
    • Wiesloch, Baden-Wuerttemberg, Germany, 69168
      • GSK Investigational Site
  • Bayern
    • Bamberg, Bayern, Germany, 96049
      • GSK Investigational Site
    • Erlangen, Bayern, Germany, 91052
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 80339
      • GSK Investigational Site
    • Muenchen, Bayern, Germany, 81241
      • GSK Investigational Site
  • Brandenburg
    • Potsdam, Brandenburg, Germany, 14469
      • GSK Investigational Site
    • Ruedersdorf, Brandenburg, Germany, 15562
      • GSK Investigational Site
  • Hessen
    • Darmstadt, Hessen, Germany, 64283
      • GSK Investigational Site
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
    • Frankfurt, Hessen, Germany, 60389
      • GSK Investigational Site
    • Frankfurt am Main, Hessen, Germany, 60596
      • GSK Investigational Site
    • Fulda, Hessen, Germany, 36039
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34121
      • GSK Investigational Site
    • Marburg, Hessen, Germany, 35037
      • GSK Investigational Site
    • Neu isenburg, Hessen, Germany, 63263
      • GSK Investigational Site
  • Mecklenburg-Vorpommern
    • Schwerin, Mecklenburg-Vorpommern, Germany, 19055
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • GSK Investigational Site
    • Hannover, Niedersachsen, Germany, 30173
      • GSK Investigational Site
    • Hannover, Niedersachsen, Germany, 30167
      • GSK Investigational Site
    • Osnabrueck, Niedersachsen, Germany, 49074
      • GSK Investigational Site
    • Peine, Niedersachsen, Germany, 31224
      • GSK Investigational Site
    • Wardenburg, Niedersachsen, Germany, 26203
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bergisch Gladbach, Nordrhein-Westfalen, Germany, 51429
      • GSK Investigational Site
    • Bochum, Nordrhein-Westfalen, Germany, 44787
      • GSK Investigational Site
    • Bonn, Nordrhein-Westfalen, Germany, 53119
      • GSK Investigational Site
    • Bonn, Nordrhein-Westfalen, Germany, 53123
      • GSK Investigational Site
    • Dortmund, Nordrhein-Westfalen, Germany, 44263
      • GSK Investigational Site
    • Dueren, Nordrhein-Westfalen, Germany, 52349
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45355
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45359
      • GSK Investigational Site
    • Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
      • GSK Investigational Site
    • Koeln, Nordrhein-Westfalen, Germany, 51069
      • GSK Investigational Site
    • Rheine, Nordrhein-Westfalen, Germany, 48431
      • GSK Investigational Site
    • Warendorf, Nordrhein-Westfalen, Germany, 48231
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Koblenz, Rheinland-Pfalz, Germany, 56068
      • GSK Investigational Site
  • Sachsen
    • Annaberg, Sachsen, Germany, 09456
      • GSK Investigational Site
    • Delitzsch, Sachsen, Germany, 04509
      • GSK Investigational Site
    • Dresden, Sachsen, Germany, 01069
      • GSK Investigational Site
    • Leipzg, Sachsen, Germany, 04109
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04275
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04357
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04103
      • GSK Investigational Site
    • Leipzig, Sachsen, Germany, 04157
      • GSK Investigational Site
    • Mittweida, Sachsen, Germany, 09648
      • GSK Investigational Site
  • Sachsen-Anhalt
    • Teuchern, Sachsen-Anhalt, Germany, 06682
      • GSK Investigational Site
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
      • GSK Investigational Site
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
    • Schleswig, Schleswig-Holstein, Germany, 24837
      • GSK Investigational Site
  • Thueringen
    • Schmoelln, Thueringen, Germany, 04626
      • GSK Investigational Site
• Italy
  • Napoli, Italy, 80131
    • GSK Investigational Site
  • San Pietro Vernotico, Italy, 72027
    • GSK Investigational Site
  • Campania
    • Benevento, Campania, Italy, 82100
      • GSK Investigational Site
    • Napoli, Campania, Italy, 80131
      • GSK Investigational Site
    • Salerno, Campania, Italy, 84131
      • GSK Investigational Site
    • San Felice A Cancello (CE), Campania, Italy, 81027
      • GSK Investigational Site
  • Emilia-Romagna
    • Reggio Emilia, Emilia-Romagna, Italy, 42100
      • GSK Investigational Site
    • Riccione (RN), Emilia-Romagna, Italy, 47838
      • GSK Investigational Site
  • Friuli-Venezia-Giulia
    • Pordenone, Friuli-Venezia-Giulia, Italy, 33170
      • GSK Investigational Site
  • Lombardia
    • Tradate (VA), Lombardia, Italy, 21049
      • GSK Investigational Site
  • Puglia
    • Cassano Delle Murge (BA), Puglia, Italy, 70020
      • GSK Investigational Site
  • Sicilia
    • Palermo, Sicilia, Italy, 90146
      • GSK Investigational Site
  • Toscana
    • Pisa, Toscana, Italy, 56124
      • GSK Investigational Site
  • Umbria
    • San Sisto (PG), Umbria, Italy, 06156
      • GSK Investigational Site
• Mexico
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • GSK Investigational Site
    • Zapopan, Jalisco, Mexico, 45070
      • GSK Investigational Site
• Netherlands
  • Almere, Netherlands, 1311 RL
    • GSK Investigational Site
  • Beek, Netherlands, 6191 JW
    • GSK Investigational Site
  • Breda, Netherlands, 4818 CK
    • GSK Investigational Site
  • Den Haag, Netherlands, 2565 KV
    • GSK Investigational Site
  • Heerlen, Netherlands, 6419 PC
    • GSK Investigational Site
  • Hoorn, Netherlands, 1624 NP
    • GSK Investigational Site
  • Kloosterhaar, Netherlands, 7694 AC
    • GSK Investigational Site
  • Rotterdam, Netherlands, 3067 GJ
    • GSK Investigational Site
  • Zutphen, Netherlands, 7207 AE
    • GSK Investigational Site
• South Africa
  • Bloemfontein, South Africa, 9301
    • GSK Investigational Site
  • Cape Town, South Africa, 7570
    • GSK Investigational Site
  • Durban, South Africa, 4001
    • GSK Investigational Site
  • Mowbray, South Africa, 7700
    • GSK Investigational Site
  • Panorama, South Africa, 7500
    • GSK Investigational Site
  • Reiger Park, South Africa, 1459
    • GSK Investigational Site
  • Gauteng
    • Eloffsdal, Gauteng, South Africa, 0084
      • GSK Investigational Site
    • Johannesburg, Gauteng, South Africa, 2113
      • GSK Investigational Site
    • Pretoria, Gauteng, South Africa, 0087
      • GSK Investigational Site
    • Pretoria, Gauteng, South Africa, 0121
      • GSK Investigational Site
  • Mpumalanga
    • Middelburg, Mpumalanga, South Africa, 1050
      • GSK Investigational Site
• Spain
  • Alicante, Spain, 03004
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08023
    • GSK Investigational Site
  • Centelles (Barcelona), Spain, 08540
    • GSK Investigational Site
  • Gerona, Spain, 17005
    • GSK Investigational Site
  • Mérida (Badajoz), Spain, 06800
    • GSK Investigational Site
  • Peralada( Girona), Spain, 17491
    • GSK Investigational Site
  • Andalucia
    • Marbella - Málaga, Andalucia, Spain, 29603
      • GSK Investigational Site
• Sweden
  • Borås, Sweden, SE-506 30
    • GSK Investigational Site
  • Göteborg, Sweden, SE-413 45
    • GSK Investigational Site
  • Göteborg, Sweden, SE-413 90
    • GSK Investigational Site
  • Höllviken, Sweden, SE-236 51
    • GSK Investigational Site
  • Linköping, Sweden, SE-587 58
    • GSK Investigational Site
  • Luleå, Sweden, SE-971 89
    • GSK Investigational Site
  • Lund, Sweden, SE-221 85
    • GSK Investigational Site
  • Lund, Sweden, SE-222 22
    • GSK Investigational Site
  • Malmö, Sweden, SE-211 52
    • GSK Investigational Site
  • Skövde, Sweden, SE-541 50
    • GSK Investigational Site
  • Stockholm, Sweden, 11446
    • GSK Investigational Site
  • Uppsala, Sweden, SE-752 37
    • GSK Investigational Site
  • Örebro, Sweden, SE-703 62
    • GSK Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85018
      • GSK Investigational Site
  • California
    • Lincoln, California, United States, 95648
      • GSK Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33765
      • GSK Investigational Site
    • Orlando, Florida, United States, 32825
      • GSK Investigational Site
    • Tampa, Florida, United States, 33603
      • GSK Investigational Site
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • GSK Investigational Site
  • Louisiana
    • Natchitoches, Louisiana, United States, 71457
      • GSK Investigational Site
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • GSK Investigational Site
    • Fridley, Minnesota, United States, 55432
      • GSK Investigational Site
    • Minneapolis, Minnesota, United States, 55407
      • GSK Investigational Site
    • Woodbury, Minnesota, United States, 55125
      • GSK Investigational Site
  • Missouri
    • Chesterfield, Missouri, United States, 63017
      • GSK Investigational Site
    • Saint Charles, Missouri, United States, 63301
      • GSK Investigational Site
    • Saint Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • Nebraska
    • Omaha, Nebraska, United States, 68134
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • GSK Investigational Site
    • Gastonia, North Carolina, United States, 28054
      • GSK Investigational Site
    • Monroe, North Carolina, United States, 28112
      • GSK Investigational Site
    • Mooresville, North Carolina, United States, 28117
      • GSK Investigational Site
    • Winston-Salem, North Carolina, United States, 27103
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • GSK Investigational Site
    • Charleston, South Carolina, United States, 29406-7108
      • GSK Investigational Site
    • Easley, South Carolina, United States, 29640
      • GSK Investigational Site
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Lancaster, South Carolina, United States, 29720
      • GSK Investigational Site
    • Mount Pleasant, South Carolina, United States, 29464
      • GSK Investigational Site
    • Rock Hill, South Carolina, United States, 29732
      • GSK Investigational Site
    • Seneca, South Carolina, United States, 29678
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Texas
    • Sherman, Texas, United States, 75092
      • GSK Investigational Site
  • Virginia
    • Abingdon, Virginia, United States, 24210
      • GSK Investigational Site
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• 40 years or older at date of signing informed consent at Screening Visit 1
• Outpatient with a diagnosis of COPD
• Persistent airflow limitations as indicated by a pre and post-albuterol/salbutamol FEV1/FVC ratio of <0.70 and a post-albuterol/salbutamol FEV1 of >=30% to <=80% predicted normal values at Screening Visit 1.
• A CAT score of >=10 at Screening Visit 1
• Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years (number of pack years = [number of cigarettes per day / 20] multiplied by number of years smoked [e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years both equal 10 pack-years]). Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1. Pipe and/or cigar use cannot be used to calculate pack-year history.
• Male and female subjects are eligible to participate in the study. A female subject is eligible to participate if she is not pregnant (as confirmed by a negative urine human chorionic gonadotrophin test), not lactating, and at least one of the following conditions applies: non-reproductive potential defined as pre-menopausal females with documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion or hysterectomy or documented bilateral oophorectomy. Postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone and estradiol levels consistent with menopause must be tested. Females on hormone replacement therapy (HRT) and whose menopausal status is in doubt will be required to use one of the highly effective contraception methods if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrolment.

A female subject with reproductive potential is eligible to participate if she is not pregnant and agrees to follow one of the highly effective methods for avoiding pregnancy in females of reproductive potential from 30 days prior to the first dose of study medication and until (at least five terminal half-lives or until any continuing pharmacologic effect has ended, whichever is longer) after the last dose of study medication and completion of the follow-up visit. The investigator is responsible for ensuring that subjects understand how to properly use methods of contraception.

• Capable of giving signed informed consent prior to study participation.

Exclusion criteria

• A current diagnosis of asthma (Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD, which is the primary cause of their respiratory symptoms).
• Subjects with known alpha-antitrypsin deficiency as the underlying cause of COPD
• Subjects with active tuberculosis are excluded. Subjects with other respiratory disorders (e.g., clinically significant: bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases) are excluded if these conditions are the primary cause of their respiratory symptoms.
• Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease as per investigator assessment); stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis; chronic stable hepatitis B and C (e.g., presence of hepatitis B surface antigen or positive hepatitis C antibody test result or within 3 months prior to first dose of study treatment) are acceptable if subject otherwise meets entry criteria.
• Subjects with unstable or life threatening cardiac disease. The investigational product should be used with caution in subjects with severe cardiovascular disease. In the opinion of the investigator, use will only be considered if the benefit is likely to outweigh the risk in conditions such as myocardial infarction or unstable angina in the last 6 months, or unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months, or New York Heart Association Class IV heart failure.
• The investigator will determine the clinical significance of each abnormal electrocardiogram (ECG) finding in relation to the subject's medical history and exclude subjects who would be at undue risk by participating in the trial. Subjects with the following abnormalities are excluded from participation in the study: atrial fibrillation with rapid ventricular rate >120 beats per minute (bpm), sustained or non-sustained ventricular tachycardia, second degree heart block Mobitz type II or third degree heart block (unless pacemaker or defibrillator had been inserted).
• Subjects with medical conditions such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy, or bladder neck obstruction will be excluded unless, in the opinion of the study physician, the benefit outweighs the risk.
• Any subject who is considered unlikely to survive the duration of the study period or has any rapidly progressing disease or immediate life-threatening illness (e.g., cancer). In addition, any subject who has any other condition (e.g., neurological condition) that is likely to affect respiratory function will not be included in the study.
• Hospitalization for COPD or pneumonia within 12 weeks prior to Visit 1. Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 14 days prior to Screening Visit 1and at least 30 days following the last dose of oral/systemic corticosteroids (if applicable).
• Subjects who had received inhaled corticosteroids (ICS) or ICS/ long-acting beta-agonist for the treatment of COPD in the 6 weeks prior to Screening Visit1.
• Subjects who had >1 moderate exacerbation in the 12 months prior to Screening Visit 1, or one severe exacerbation requiring hospitalization in the 12 months prior to Screening Visit 1.
• Other respiratory tract infections that have not resolved at least 7 days prior to Screening Visit 1.
• Subjects with lung volume reduction surgery (including procedures such as endobronchial valves) within the 12 months prior to Screening Visit 1.
• Use of long-term oxygen therapy described as resting oxygen therapy >3 Liter (L)/minute (min) at screening required to maintain adequate oxygenation (e.g., oxygen saturation in arterial blood [SaO2] >90%; oxygen use <=3 L/min flow is not exclusionary, and subjects may adjust oxygen levels up or down as needed during the study.)
• Use of ICS within 6 weeks prior to Screening Visit 1; use of depot corticosteroids within 12 weeks prior to Screening Visit 1; use of systemic, oral or parenteral corticosteroids within 6 weeks prior to Screening Visit 1 (Localized corticosteroid injections [e.g., intra-articular and epidural] are permitted); use of antibiotics (for lower respiratory tract infection) within 6 weeks prior to Screening Visit 1; use of phosphodiesterase 4 (PDE4) inhibitor (e.g., roflumilast) within 14 days prior to Screening Visit 1; use of long-acting beta-agonist/ ICS combination products within 6 weeks prior to Screening Visit 1; use of theophyllines within 48 hours prior to Screening Visit 1; use of oral long-acting beta2-agonists within 48 hours and short-acting beta2-agonists within 12 hours prior to Screening Visit 1; use of inhaled short-acting beta2-agonists within 4 hours prior to Screening Visit 1 (use of study provided albuterol/salbutamol is permitted during the study, except in the 4-hour period prior to spirometry testing); use of inhaled short-acting anticholinergics within 4 hours prior to Screening Visit 1; use of inhaled short-acting anticholinergic/short-acting beta2-agonist combination products within 4 hours prior to Screening Visit 1; use of any other investigational medication within 30 days or within 5 drug half-lives (whichever is longer) prior to Screening Visit 1.
• Subject unable to withhold albuterol/salbutamol for the 4-hour period required prior to spirometry testing at each study visit.
• Regular use (prescribed for daily/ regular use, not for as-needed use) of short-acting bronchodilators (e.g., albuterol/salbutamol).
• A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit 1 that in the opinion of the investigator would prevent the subject from completing the study procedures.
• Any history of allergy or hypersensitivity to any anticholinergic/muscarinic receptor antagonist, sympathomimetic, lactose/milk protein or magnesium stearate.
• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
• Subject is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.
• In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete questionnaires on the electronic diary.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UMEC/VI 62.5/25 mcg via ELLIPTA + placebo via DISKUS; Subjects will be instructed to self-administer one dose of UMEC/VI 62.5/25 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.	Drug: UMEC/VI 62.5/25 mcg via ELLIPTA; ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; the first strip contains umeclidinium bromide (62.5 mcg per blister) blended with lactose monohydrate and magnesium stearate and second strip contains vilanterol trifenatae (25 mcg per blister) blended with lactose monohydrate and magnesium stearate.; Drug: Placebo via DISKUS; Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.
Experimental: UMEC 62.5 mcg via ELLIPTA + placebo via DISKUS; Subjects will be instructed to self-administer one dose of UMEC 62.5 mcg inhalation powder each morning via ELLIPTA DPI and placebo twice daily (morning and evening) via DISKUS DPI.	Drug: Placebo via DISKUS; Lactose dry powder will be administered using DISKUS for both treatment periods. The DISKUS inhaler will contain one blister strip, which will have 60 blisters of lactose dry powder. The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.; Drug: UMEC 62.5 mcg via ELLIPTA; The ELLIPTA inhaler will contain one blister strip, which will have 30 blisters of umeclidinium bromide (62.5 mcg).
Experimental: Salmeterol 50 mcg via DISKUS + placebo via ELLIPTA; Subjects will be instructed to self-administer one dose of salmeterol 50 mcg twice daily (morning and evening) via DISKUS DPI and placebo once daily morning via ELLIPTA DPI.	Drug: Salmeterol 50 mcg via DISKUS; The DISKUS inhaler will contain one blister strip, which will have 60 blisters of salmeterol xinafoate (50 mcg). The DISKUS will provide a total of 60 doses (60 blisters) and will deliver, when actuated, the contents of a single blister strip.; Drug: Placebo via ELLIPTA; Lactose dry powder will be administered using ELLIPTA for both treatment periods. ELLIPTA DPI inhaler will contain two individual blister strips with 30 blisters per strip; containing lactose dry powder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 at Week 24 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on the previous day. Baseline trough FEV1 is the mean of the values measured at 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as the trough FEV1 value on Week 24 minus the Baseline value. Analysis was performed using a repeated measures model (MMRM) with covariates of Baseline FEV1, geographical region, stratum (number of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interaction. ITT population comprised of all randomized participants (excluding those who were randomized in error) who received at least one dose of study medication.	Baseline (Pre-dose on Day 1) and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Self Administered Computerized (SAC) Transient Dyspnea Index (TDI) Focal Score at Week 24	TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then the TDI focal score was set to missing. Analysis was performed using mixed model repeated measures (MMRM) with covariates of SAC BDI focal score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by SAC BDI and visit by treatment interactions.	Week 24
Percentage of TDI Responders According to SAC TDI Focal Score	TDI focal score comprises of 3 individual scales (Functional Impairment, Magnitude of Task, Magnitude of Effort). Each of these scales had a possible score ranging from -6 to +6, lower scores indicates impairment. TDI focal score was calculated as the sum of 3 individual scores (range is -18 to +18). Lower score indicates deterioration of dyspnea. If a score is missing for any of the three scales, then TDI focal score was set to missing. A participant was considered as a responder if the on-treatment TDI focal score was at least 1 unit at that visit. Non-response was SAC TDI focal score of less than 1 unit or a missing SAC TDI focal score with no subsequent non-missing on-treatment scores. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, SAC BDI focal score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by SAC BDI and visit by treatment interactions included as covariates.	Week 24
Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score	The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.	Baseline (Pre-dose on Day 1) and Week 21 to Week 24
Mean Change From Baseline in E-RS Subscale Score	The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: respiratory symptoms (RS)-breathlessness (RS-BRL comprised of 5 items, score range [0-17]), RS-cough and sputum (RS-CSP comprised of 3 items, score range [0-11]), and RS-chest symptoms (RS-CSY comprised of 3 items, score range [0-12]). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Baseline E-RS score is the mean within-participant daily score over 7 days prior to randomization. Change from Baseline is the difference at Week 21-Week 24 value and Baseline value. Analysis was performed using MMRM with covariates of Baseline score, geographical region, stratum (no. of bronchodilators per day during run-in), 4-weekly period, treatment, 4-weekly period by Baseline and 4-weekly period by treatment interactions.	Baseline (Pre-dose on Day 1) and Week 21 to Week 24
Percentage of E-RS Responders According to E-RS Total Score	The E-RS is intended to capture information related to respiratory symptoms. A daily symptom score for E-RS is derived by summing 11 item-scores. The domains include: RS-BRL comprised of 5 items, score range (0-17); RS-CSP comprised of 3 items, score range (0-11); and RS-CSY comprised of 4 items, score range (0-12). Total score ranged between 0-40 and higher values indicates severe respiratory symptoms. The instrument was completed each night prior to going to bed. Response is defined as an E-RS total score of at least 2 or 3.35 below Baseline. Participants with a Baseline but all missing post-Baseline data are also considered a non-responder. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and four-weekly period, Baseline score, stratum (no. of bronchodilators per day during run-in), geographical region, four-weekly period by baseline and four-weekly period by treatment interactions included as covariates.	Week 21 to Week 24
Change From Baseline in St George's Respiratory Questionnaire (SGRQ) Total Score	SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Baseline is last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline SGRQ total score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.	Baseline (Pre-dose on Day 1) and Week 24
Percentage of Responders Based on the Saint (St) George Respiratory Questionnaire COPD Specific (SGRQ) Total Score	SGRQ is a disease-specific questionnaire designed to measure impact of respiratory disease and its treatment on HRQoL of participants with COPD. It contains 14 questions with a total of 40 items grouped into domains (Symptoms, Activity and Impacts). SGRQ total score was calculated as 100 multiplied by summed weights from all positive items divided by sum of weights for all items in questionnaire. It ranges from 0 to 100, higher score indicates poor HRQoL. Analysis was performed using a generalized linear mixed model with treatment as an explanatory variable and visit, Baseline SGRQ score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by Baseline and visit by treatment interactions included as covariates. Response was defined as an SGRQ total score of 4 or more units below Baseline.	Week 24
Change From Baseline in COPD Assessment Test (CAT)	The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items, each formatted on a differential scale. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicating greater disease impact. Baseline is defined as the last non-missing score recorded prior to dosing on Day 1. Change from Baseline was calculated by subtracting Baseline value from the value at Week 24. Analysis was performed using mixed model repeated measures (MMRM) with covariates of Baseline CAT score, geographical region, stratum (no. of bronchodilators per day during run-in), visit, treatment, visit by Baseline and visit by treatment interactions.	Baseline (Pre-dose on Day 1) and Week 24
Percentage of Responders According to CAT	The CAT is a participant-completed instrument designed to provide a simple and reliable measure of health status in COPD for the assessment and long-term follow-up of the individual participant. The CAT consists of eight items. Participants rated their experience on a 6-point scale for each question, ranging from 0 (no impact) to 5 (high impact). A total CAT score was calculated by summing the non-missing scores on the eight items ranging from 0 to 40 with higher scores indicate greater disease impact. Response was defined as an CAT score of >=2 below Baseline. Non response was defined as CAT score <2 units below Baseline or a missing CAT score with no subsequent on treatment scores. Analysis performed using a generalized linear mixed model with treatment as an explanatory variable and visit, baseline CAT score, stratum (no. of bronchodilators per day during run-in), geographical region, visit by baseline and visit by treatment interactions included as covariates.	Week 24
Number of Participants With on Treatment Adverse Events (AE) and Serious Adverse Events (SAE)	An AE is any untoward medical occurrence in a participant or clinical investigation participant , temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events associated with liver injury and impaired liver function based on pre-defined criteria were categorized as SAE.	Up to Week 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Maltais F, Bjermer L, Kerwin EM, Jones PW, Watkins ML, Tombs L, Naya IP, Boucot IH, Lipson DA, Compton C, Vahdati-Bolouri M, Vogelmeier CF. Efficacy of umeclidinium/vilanterol versus umeclidinium and salmeterol monotherapies in symptomatic patients with COPD not receiving inhaled corticosteroids: the EMAX randomised trial. Respir Res. 2019 Oct 30;20(1):238. doi: 10.1186/s12931-019-1193-9.
• Bjermer LH, Boucot IH, Vogelmeier CF, Maltais F, Jones PW, Tombs L, Compton C, Lipson DA, Kerwin EM. Efficacy and Safety of Umeclidinium/Vilanterol in Current and Former Smokers with COPD: A Prespecified Analysis of The EMAX Trial. Adv Ther. 2021 Sep;38(9):4815-4835. doi: 10.1007/s12325-021-01855-y. Epub 2021 Aug 4.
• Maltais F, Naya IP, Vogelmeier CF, Boucot IH, Jones PW, Bjermer L, Tombs L, Compton C, Lipson DA, Kerwin EM. Salbutamol use in relation to maintenance bronchodilator efficacy in COPD: a prospective subgroup analysis of the EMAX trial. Respir Res. 2020 Oct 22;21(1):280. doi: 10.1186/s12931-020-01451-8.
• Kerwin EM, Boucot IH, Vogelmeier CF, Maltais F, Naya IP, Tombs L, Jones PW, Lipson DA, Keeley T, Bjermer L. Early and sustained symptom improvement with umeclidinium/vilanterol versus monotherapy in COPD: a post hoc analysis of the EMAX randomised controlled trial. Ther Adv Respir Dis. 2020 Jan-Dec;14:1753466620926949. doi: 10.1177/1753466620926949.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2017
• Primary Completion (Actual): June 18, 2018
• Study Completion (Actual): June 18, 2018

Study Registration Dates

• First Submitted: January 25, 2017
• First Submitted That Met QC Criteria: January 25, 2017
• First Posted (Estimate): January 27, 2017

Study Record Updates

• Last Update Posted (Actual): March 11, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: COPD; Salmeterol; HRQoL; Vilanterol; Umeclidinium
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Salmeterol Xinafoate
• Other Study ID Numbers: 201749; 2016-002513-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No