Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level

Pulmonary Disease, Chronic Obstructive Clinical Trial

— MATINEE  

Official title:

A Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Mepolizumab 100 mg SC as add-on Treatment in Participants With COPD Experiencing Frequent Exacerbations and Characterized by Eosinophil Levels (Study 208657)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04133909
• Other study ID #: 208657
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 30, 2019
• Est. completion date: August 19, 2024

Study information

• Verified date: August 2023
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study designed to confirm the benefits of mepolizumab treatment on moderate or severe exacerbations in chronic obstructive pulmonary disease (COPD) participants given as an add on to their optimized maintenance COPD therapy. The maximum duration of participant participation is approximately 109 weeks, consisting of 2 screening visits (up to 3 weeks), a run-in period (up to 2 weeks), and an intervention period of at least 52 weeks and up to 104 weeks. 800 participants will be randomized in a 1:1 ratio to receive mepolizumab 100 milligrams (mg) or placebo every 4 weeks for at least 13 doses (52 weeks treatment period) up to a maximum of 26 doses (104 weeks treatment period). The number of randomized participants may increase up to approximately 1400.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 806
• Est. completion date: August 19, 2024
• Est. primary completion date: August 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• Participant must be at least 40 years of age at Screening Visit 1.

• Participants with a peripheral blood eosinophil count of >=300 cells per microliter (µL) from the hematology sample collected at Screening Visit 0 AND a documented historical blood eosinophil count of >=150 cells per µL in the 12 months prior to Screening Visit 0 that meets the following: It must have been measured between 12 months and 1 month prior to Screening Visit 0, and it must not have been measured within 14 days of a COPD exacerbation. Participants with no documented historical blood eosinophil count of >=150 cells per µL must meet this threshold at the Screening Visit 1 assessment.

• Participants with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society or European Respiratory Society.

• Participants must present with a measured pre- and post-salbutamol Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio of <0.70 at Screening Visit 1 to confirm the diagnosis of COPD and with a measured post-salbutamol FEV1>20% and <=80% of predicted normal values calculated using NHANES III reference equations at Screening Visit 1.

• Participants must have a well-documented history (for example, medical record verification) in the 12 months prior to Screening Visit 1 of two or more moderate COPD exacerbations that were treated with systemic corticosteroids (intramuscular [IM], intravenous, or oral) with or without antibiotics or at least one severe COPD exacerbation requiring hospitalization.

• Participants must have a well-documented requirement for optimized standard of care background therapy that includes inhaled corticosteroids (ICS) plus 2 additional COPD medications (ICS-based triple therapy) for the 12 months prior to Screening Visit 1 and meets the following criteria: immediately prior to Screening Visit 1, minimum of 3 months of use of an 1) inhaled corticosteroid at a dose >=500 microgram (mcg) per day fluticasone propionate dose equivalent plus 2) Long acting beta2-agonist (LABA) and 3) Long acting muscarinic antagonist (LAMA) unless documentation of safety or intolerance issues related to LABA or LAMA. For participants who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of the following is allowed (but not in the 3 months immediately prior to Visit 1); inhaled corticosteroid at a dose >=500 mcg per day fluticasone propionate dose equivalent plus inhaled LABA or inhaled LAMA and Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of short acting beta2-agonist (SABA) and/or short acting muscarinic antagonist (SAMA).

• Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Screening (Visit 1) calculated as (number of pack years = [number of cigarettes per day/20] multiplied by number of years smoked [For example, 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years]).

• Contraceptive use for female participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

• A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is not a woman of childbearing potential (WOCBP) or she is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of <1%, during the intervention period and for at least 16 weeks after the last dose of study intervention. The principal investigator (PI) should evaluate the effectiveness of the contraceptive method in relation to the first dose of study intervention.

• A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (For example, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

• Participants capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

• Participants must meet following randomization inclusion criteria at Visit 2 to be randomized and commence the study intervention period: a) Participants that do not have documented historical blood eosinophil count of =150 cells/µL prior to Screening Visit must meet this threshold based on the Screening Visit 1 assessment, b) Participants must have eosinophil count of =300 cells/µL from the hematology sample collected at Screening Visit 0, c) Compliance with completion of the e-diary defined as completion of all questions on 5 or more days out of the 7 days immediately preceding Visit 2.

Exclusion Criteria:

• Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease.

• The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Participants with alpha1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

• Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1.

• Participants with lung volume reduction surgery within the 12 months prior to Screening Visit 1.

• Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Participants who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.

• Participants receiving treatment with oxygen more than 2 liter (L) per minute at rest over 24 hours. For participants receiving oxygen treatment, participants should demonstrate an oxyhemoglobin saturation greater than or equal to 89% while breathing supplemental oxygen.

• Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) >450 millisecond (msec) (or QTcF >480 msec in participants with bundle branch block). Fridericia's formula must be used to determine eligibility and discontinuation for an individual participant. Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the participant's participation during the study, based on the evaluation of the Investigator.

• Participants with any of the following would be excluded: myocardial infarction or unstable angina in the 6 months prior to Screening Visit 1; unstable or life threatening cardiac arrhythmia requiring intervention in the 3 months prior to Screening Visit 1; New York Heart Association (NYHA) Class IV Heart failure.

• Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

• Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA), also known as Churg-Strauss Syndrome, or Eosinophilic Esophagitis.

• Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1.

• A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded).

• Participants with a known immunodeficiency (For example, human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids taken for COPD.

• Participants with cirrhosis or current unstable liver disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice. Stable non-cirrhotic chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C -e.g., presence of hepatitis B surface antigen [HbsAg] or positive hepatitis C antibody test result) is acceptable if the participant otherwise meets entry criteria.

• Participants who have received interventional product in previous mepolizumab studies are excluded.

• Participants who have received any monoclonal antibody within 5 half-lives of Screening Visit 1.

• Participants who have received an investigational drug within 30 days of Visit 1, or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).

• Participants who have received short term use of oral corticosteroids within 30 days of Visit 1.

• Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.

• Participants at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

• Participants with conditions that will limit the validity of informed consent to participate in the study, for example, uncontrolled psychiatric disease or intellectual deficiency.

• Participants with a known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.

• Participant 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.

• Participants with a current active COVID-19 infection, either laboratory confirmed or according to the investigator's medical judgement and who are known to be in contact with active COVID-19 positive individuals within the past 14 days.

• Participant will not be randomized if they meet any of the following randomization exclusion criteria at Visit 2: a) Participants who have pneumonia, exacerbation, lower respiratory infection during the Run-in period. b) Evidence of clinically significant abnormality in the hematological or biochemical screen at Visit 1, as judged by the Investigator. c) Participants who meet the following based on results from sample taken at Screening Visit 1: Alanine aminotransferase (ALT) >2x upper limit of normal (ULN), bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%), cirrhosis or current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice. d) Participants who are pregnant or breastfeeding. Participants should not be randomized if they plan to become pregnant during the time of study participation. e) Participants that had an active COVID-19 infection during the Run-in period, either laboratory confirmed or according to the investigator's medical judgment or known to be in contact with active COVID-19 positive individuals within the past 14 days. f) Participants with a QT interval, from the ECG conducted at Visit 2, corrected with Fridericia's formula (QTcF) >450 msec (or QTcF >480 msec in participants with bundle branch block).

Related Conditions & MeSH terms

• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Placebo
Placebo is a 0.9% sodium chloride solution. It will be administered as a subcutaneous (SC) injection delivered once every 4 weeks using a pre-filled safety syringe.

Biological:
• Mepolizumab
Mepolizumab is a sterile liquid formulation. It will be administered as a SC injection (100 mg/mL) delivered once every 4 weeks using a pre-filled safety syringe.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Berazategui, Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad de Buenos Aires
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	La Plata
Argentina	GSK Investigational Site	Lobos	Buenos Aires
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mar Del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Fernando	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucumán
Argentina	GSK Investigational Site	San Miguel de Tucumán	Tucumán
Argentina	GSK Investigational Site	San Rafael	Mendoza
Australia	GSK Investigational Site	Coffs Harbour	New South Wales
Australia	GSK Investigational Site	Frankston	Victoria
Australia	GSK Investigational Site	Kent Town	South Australia
Australia	GSK Investigational Site	New Lambton	New South Wales
Australia	GSK Investigational Site	Sydney	New South Wales
Australia	GSK Investigational Site	Westmead	New South Wales
Australia	GSK Investigational Site	Woodville South	South Australia
Austria	GSK Investigational Site	Wien
Belgium	GSK Investigational Site	Jambes
Belgium	GSK Investigational Site	Liège
Belgium	GSK Investigational Site	Yvoir
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Porto Alegre	Rio Grande Do Sul
Brazil	GSK Investigational Site	Santo Andre	São Paulo
Brazil	GSK Investigational Site	São Paulo
Canada	GSK Investigational Site	Ajax	Ontario
Canada	GSK Investigational Site	Newmarket	Ontario
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	St. Charles-Borromee	Quebec
Canada	GSK Investigational Site	Truro	Nova Scotia
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	Windsor	Ontario
China	GSK Investigational Site	Baotou	Inner Mongolia
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Beijing
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changchun	Jilin
China	GSK Investigational Site	Changsha
China	GSK Investigational Site	Changsha
China	GSK Investigational Site	Changsha
China	GSK Investigational Site	Changsha	Hunan
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Guangzhou	Guangdong
China	GSK Investigational Site	Haikou	Hainan
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hohehot
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Nanchang
China	GSK Investigational Site	Nanchang
China	GSK Investigational Site	Nanchang
China	GSK Investigational Site	Nanjing
China	GSK Investigational Site	Nanjing
China	GSK Investigational Site	Nanning	Guangxi
China	GSK Investigational Site	Qingdao	Shandong
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Taiyuan	Shanxi
China	GSK Investigational Site	Taizhou
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Urumqi	Xinjiang
China	GSK Investigational Site	Wuxi	Jiangsu
China	GSK Investigational Site	Xiamen	Fujian
China	GSK Investigational Site	Xining
China	GSK Investigational Site	Zhuhai
Denmark	GSK Investigational Site	Aalborg
Denmark	GSK Investigational Site	Hvidovre
Denmark	GSK Investigational Site	Kobenhavn NV
Denmark	GSK Investigational Site	København Ø
Denmark	GSK Investigational Site	Odense
Denmark	GSK Investigational Site	Rosklide
Denmark	GSK Investigational Site	Vejle
France	GSK Investigational Site	Brest cedex
France	GSK Investigational Site	Cholet
France	GSK Investigational Site	Clermont-Ferrand
France	GSK Investigational Site	Le Mans
France	GSK Investigational Site	Lyon
France	GSK Investigational Site	Montpellier cedex 5
France	GSK Investigational Site	Mulhouse
France	GSK Investigational Site	Pringy Cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Frankfurt	Hessen
Germany	GSK Investigational Site	Geesthacht	Schleswig-Holstein
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Halle	Sachsen-Anhalt
Germany	GSK Investigational Site	Immenhausen	Hessen
Germany	GSK Investigational Site	Koblenz	Rheinland-Pfalz
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Leipzig	Sachsen
Germany	GSK Investigational Site	Luebeck	Schleswig-Holstein
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Neu-Isenburg	Hessen
Germany	GSK Investigational Site	Peine	Niedersachsen
Germany	GSK Investigational Site	Rheine	Nordrhein-Westfalen
Germany	GSK Investigational Site	Rodgau	Hessen
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Germany	GSK Investigational Site	Stuttgart
Greece	GSK Investigational Site	Alexandroupolis
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athina
Greece	GSK Investigational Site	Ioannina
Greece	GSK Investigational Site	Patras
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Debrecen
Hungary	GSK Investigational Site	Gyula
Hungary	GSK Investigational Site	Hajdunanas
Hungary	GSK Investigational Site	Hatvan
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Siófok
Hungary	GSK Investigational Site	Törökbálint
Hungary	GSK Investigational Site	Zalaegerszeg
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Aligarh
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Kanpur
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	Madurai
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Secunderabad
Ireland	GSK Investigational Site	Drogheda
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	Dublin
Ireland	GSK Investigational Site	Dublin 15
Ireland	GSK Investigational Site	Galway
Ireland	GSK Investigational Site	Limerick
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Beer-Yaakov
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Petah Tikva
Israel	GSK Investigational Site	Ramat Gan
Israel	GSK Investigational Site	Rehovot
Italy	GSK Investigational Site	Ferrara	Emilia-Romagna
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Telese Terme (BN)	Campania
Italy	GSK Investigational Site	Verona	Veneto
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Gunma
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Mie
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shizuoka
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Jeonju-si, Jeollabuk-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Jalisco
Mexico	GSK Investigational Site	Mexico City
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Den Haag
Netherlands	GSK Investigational Site	Groningen
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Rotterdam
Netherlands	GSK Investigational Site	Zutphen
New Zealand	GSK Investigational Site	Auckland
New Zealand	GSK Investigational Site	Hamilton
New Zealand	GSK Investigational Site	Havelock North
New Zealand	GSK Investigational Site	Rotorua
New Zealand	GSK Investigational Site	Wellington
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Elblag
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdynia
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Ostrow Wilekopolski
Poland	GSK Investigational Site	Ostrowiec Swietokrzyski
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Sopot
Poland	GSK Investigational Site	Sosnowiec
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zamosc
Spain	GSK Investigational Site	Alzira/Valencia
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Benalmadena Costa
Spain	GSK Investigational Site	Caceres
Spain	GSK Investigational Site	Cádiz
Spain	GSK Investigational Site	Galdakano
Spain	GSK Investigational Site	Granada
Spain	GSK Investigational Site	Guadalajara
Spain	GSK Investigational Site	L'Hospitalet de Llobregat
Spain	GSK Investigational Site	Lleida
Spain	GSK Investigational Site	Logroño
Spain	GSK Investigational Site	Loja/ Granada
Spain	GSK Investigational Site	Marbella - Málaga	Andalucia
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Sagunto/Valencia
Spain	GSK Investigational Site	Salamanca	Castilla Y Leon
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Zaragoza
Sweden	GSK Investigational Site	Härnösand
Sweden	GSK Investigational Site	Malmö
Sweden	GSK Investigational Site	Uppsala
Taiwan	GSK Investigational Site	Taipei
United Kingdom	GSK Investigational Site	Birmingham
United Kingdom	GSK Investigational Site	Buckshaw Village, Chorley	Lancashire
United Kingdom	GSK Investigational Site	Cardiff
United Kingdom	GSK Investigational Site	Dundee
United Kingdom	GSK Investigational Site	Glasgow
United Kingdom	GSK Investigational Site	Gwaelod-y-Garth, Cardiff
United Kingdom	GSK Investigational Site	Hexham
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Norwich
United Kingdom	GSK Investigational Site	Stockton On Tees
United Kingdom	GSK Investigational Site	Wishaw	Lanarkshire
United States	GSK Investigational Site	Adairsville	Georgia
United States	GSK Investigational Site	Albuquerque	New Mexico
United States	GSK Investigational Site	Anderson	South Carolina
United States	GSK Investigational Site	Baltimore	Maryland
United States	GSK Investigational Site	Birmingham	Alabama
United States	GSK Investigational Site	Boynton Beach	Florida
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Cerritos	California
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Charleston	South Carolina
United States	GSK Investigational Site	Chicago	Illinois
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Clearwater	Florida
United States	GSK Investigational Site	Clinton	South Carolina
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Columbus	Ohio
United States	GSK Investigational Site	Conway	Arkansas
United States	GSK Investigational Site	Corsicana	Texas
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Daytona Beach	Florida
United States	GSK Investigational Site	Doral	Florida
United States	GSK Investigational Site	Dothan	Alabama
United States	GSK Investigational Site	DuBois	Pennsylvania
United States	GSK Investigational Site	Evansville	Indiana
United States	GSK Investigational Site	Fort Mill	South Carolina
United States	GSK Investigational Site	Fort Pierce	Florida
United States	GSK Investigational Site	Gaffney	South Carolina
United States	GSK Investigational Site	Gainesville	Florida
United States	GSK Investigational Site	Gastonia	North Carolina
United States	GSK Investigational Site	Gilbert	Arizona
United States	GSK Investigational Site	Glendale	Arizona
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Henderson	Nevada
United States	GSK Investigational Site	Hickory	North Carolina
United States	GSK Investigational Site	Homestead	Florida
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jasper	Alabama
United States	GSK Investigational Site	Johns Creek	Georgia
United States	GSK Investigational Site	Kettering	Ohio
United States	GSK Investigational Site	Knoxville	Tennessee
United States	GSK Investigational Site	Lampasas	Texas
United States	GSK Investigational Site	Lancaster	South Carolina
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lathrup Village	Michigan
United States	GSK Investigational Site	Lawrenceville	Georgia
United States	GSK Investigational Site	Lexington	Kentucky
United States	GSK Investigational Site	McAllen	Texas
United States	GSK Investigational Site	McKinney	Texas
United States	GSK Investigational Site	Melbourne	Florida
United States	GSK Investigational Site	Mesa	Arizona
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Natchitoches	Louisiana
United States	GSK Investigational Site	New Port Richey	Florida
United States	GSK Investigational Site	Newport Beach	California
United States	GSK Investigational Site	Norman	Oklahoma
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Orlando	Florida
United States	GSK Investigational Site	Palm Springs	California
United States	GSK Investigational Site	Philadelphia	Pennsylvania
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Phoenix	Arizona
United States	GSK Investigational Site	Pinellas Park	Florida
United States	GSK Investigational Site	Plantation	Florida
United States	GSK Investigational Site	Port Orange	Florida
United States	GSK Investigational Site	Portland	Oregon
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rock Hill	South Carolina
United States	GSK Investigational Site	Rutland	Vermont
United States	GSK Investigational Site	Saint Louis	Missouri
United States	GSK Investigational Site	Saint Petersburg	Florida
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Sheffield	Alabama
United States	GSK Investigational Site	Shelby	North Carolina
United States	GSK Investigational Site	Sherman	Texas
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	Sugar Land	Texas
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	Tampa	Florida
United States	GSK Investigational Site	The Villages	Florida
United States	GSK Investigational Site	Toms River	New Jersey
United States	GSK Investigational Site	Torrance	California
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Valparaiso	Indiana
United States	GSK Investigational Site	Vista	California
United States	GSK Investigational Site	Webster	Texas
United States	GSK Investigational Site	Wilmington	North Carolina
United States	GSK Investigational Site	Winston-Salem	North Carolina
United States	GSK Investigational Site	Woodstock	Georgia

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	PPD

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  New Zealand,  Poland,  Spain,  Sweden,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized rate of moderate or severe exacerbations	Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (>=24 hours) or result in death. The frequency of moderate or severe exacerbations expressed as an annualized exacerbation rate will be evaluated.	Up to Week 104
Secondary	Time to first moderate or severe exacerbation	Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization (>=24 hours) or result in death.	Up to Week 104
Secondary	Number of COPD assessment test (CAT) responders	The proportion of CAT score responders with reduction of >=2 units in CAT score from Baseline will be assessed.	Week 52
Secondary	Number of St. George's Respiratory Questionnaire (SGRQ) total score responders	The proportion of SGRQ total score responders with reduction of >=4 units in SGRQ total score from Baseline will be assessed. It will be calculated using St. George's Respiratory Questionnaire for COPD (SGRQ-C).	Week 52
Secondary	Number of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) responders	The proportion of E-RS: COPD responders with reduction of >=2 units in E-RS: COPD total score from Baseline will be assessed.	Week 52
Secondary	Annualized rate of exacerbations requiring Emergency Department (ED) visit or hospitalization	Annualized rate of exacerbations requiring ED visit or hospitalization will be evaluated.	Up to Week 104