Study to Evaluate the Effect of Fluticasone Furoate/Vilanterol on Survival in Subjects With Chronic Obstructive Pulmonary Disease

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Clinical Outcomes Study to Compare the Effect of Fluticasone Furoate/Vilanterol Inhalation Powder 100/25mcg With Placebo on Survival in Subjects With Moderate Chronic Obstructive Pulmonary Disease (COPD) and a History of or at Increased Risk for Cardiovascular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01313676
• Other study ID #: 113782
• Status: Completed
• Phase: Phase 3
• Start date: January 25, 2011
• Est. completion date: July 15, 2015

Study information

• Verified date: August 2018
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if fluticasone furoate/vilanterol improves survival in patients with chronic obstructive pulmonary disease with a history of or increased risk of heart disease.

Description:

Despite a potential link between the pathogenetic mechanisms involved in Chronic Obstructive Pulmonary Disease (COPD) and atherosclerotic cardiovascular disease, there are no currently approved therapies for patients with COPD that have clearly shown an additional beneficial effect in patients with cardiovascular comorbidities. The TOwards a Revolution in COPD Health (TORCH) study assessed the impact of the inhaled corticosteroid (ICS) fluticasone propionate (FP) in combination with the long-acting beta agonist (LABA), salmeterol (SAL), in reducing all-cause mortality. TORCH demonstrated a 17.5% reduction on all-cause mortality with salmeterol-fluticasone propionate combination (SFC) compared with placebo (HR=0.825, 95% CI (0.681, 1.002), p=0.052) in the entire COPD population with disease severity form moderate to very severe. A post hoc analysis of the data restricted to those subjects with an forced expiratory volume in 1 second (FEV1) >=50% predicted with an apparent history of cardiovascular co-morbidities (defined as use at baseline of beta-blockers, angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), HMG CoA reductase inhibitors (i.e. statins) or a prior MI recorded at baseline) demonstrated a 49% reduction in the risk of dying within 96 weeks for the comparison of SFC with placebo. These post hoc data suggest the possibility of an ICS/LABA combination product to be of substantial benefit in COPD subjects with less severe airflow obstruction yet with increased cardiovascular risk.

The mechanism by which SFC appears to be associated with a greater reduction in mortality in these less severe COPD subjects with concomitant cardiovascular comorbidities is speculative at present, but could potentially in part be related to a lessening of the degree of inflammation in the systemic circulation, potential plaque stabilization and/or amelioration of arterial stiffness.

ICS/LABA combinations that are currently available require twice daily administration. A once daily ICS/LABA combination has the potential to improve patient compliance and as a result, overall disease management.

The purpose of this study is to prospectively evaluate the effect of the once daily ICS/LABA combination Fluticasone Furoate (FF)/Vilanterol (VI) on survival in subjects with moderate COPD (>=50 and =<70 % predicted FEV1 ) and a history of, or at increased risk for cardiovascular disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16568
• Est. completion date: July 15, 2015
• Est. primary completion date: July 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

Inclusion Criteria:

• Type of subject: outpatient.

• Informed consent: Subjects must give their signed and dated written informed consent to participate.

• Gender: Male or female. Female subjects must be post-menopausal or using a highly effective method for avoidance of pregnancy. The decision to include or exclude women of childbearing potential may be made at the discretion of the investigator in accordance with local practice in relation to adequate contraception.

• Age: >=40 and <=80 years of age at Screening (Visit 1).

• Tobacco use: Subjects with a current or prior history of >=10 pack-years of cigarette smoking at screening (Visit 1). Previous smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 1.

• Airflow Obstruction:

Subjects with a measured post-albuterol/salbutamol forced expiratory volume in 1 second (FEV1)/(forced vital capacity)FVC ratio of <=0.70 at Screening (Visit 1).

Subjects with a measured post-albuterol/salbutamol FEV1 >=50 and <=70% of predicted normal values calculated using NHANES III reference equations [Hankinson, 1999; Hankinson, 2010] at Screening (Visit 1).

Post-bronchodilator spirometry will be performed approximately 15 minutes after the subject has self-administered 4 inhalations (i.e., total 400mcg) of albuterol/salbutamol via a metered dose inhaler (MDI )with a valved-holding chamber. The FEV1/FVC ratio and FEV1 percent predicted values will be calculated.

• Symptoms of COPD: Subjects must score 2 or higher on the modified Medical Research Council Dyspnea scale (Visit 1)

• Cardiovascular disease:

For patients >= 40 years of age: any one of the following:

Established (i.e. by clinical signs or imaging studies) coronary artery disease (CAD) Established (i.e. by clinical signs or imaging studies) peripheral vascular disease (PVD) Previous stroke Previous MI Diabetes mellitus with target organ disease OR

For patients >=60 years of age: any 2 of the following:

Being treated for hypercholesterolemia Being treated for hypertension Being treated for diabetes mellitus Being treated for peripheral vascular disease

Exclusion Criteria:

• Pregnancy: Women who are pregnant or lactating.

• Asthma: Subjects with a current diagnosis of asthma. (Subjects with a prior history of asthma are eligible if they also have a current diagnosis of COPD).

• alpha 1-antitrypsin deficiency: Subjects with known alpha-1 antitrypsin deficiency as the underlying cause of COPD.

• Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, pulmonary fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases.

• Lung resection or transplantation: Subjects with lung volume reduction surgery within the 12 months prior to Screening or having had a lung transplant.

• A moderate/severe COPD exacerbation that has not resolved at least 14 days prior to Visit 1 and at least 30 days following the last dose of oral corticosteroids (if applicable).

• Current severe heart failure (New York Heart Association class IV). Subjects will also be excluded if they have a known ejection fraction of <30% or if they have an implantable cardioverter defibrillator (ICD).

• Other diseases/abnormalities: Any life-threatening condition with life expectancy <3 years, other than vascular disease or COPD, that might prevent the subject from completing the study.

• End stage chronic renal disease: Subjects will be excluded if on renal replacement therapy (hemodialysis or peritoneal).

• Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medications (e.g. beta-agonists, corticosteroid) or components of the inhalation powder (e.g. lactose, magnesium stearate). In addition, patients with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates the subject's participation will also be excluded.

• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years.

• Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e. <=12 hours per day) is not exclusionary.

• Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study or the potential compliance to study procedures.

• Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

• Additional medication: Use of the following medications within the following time intervals prior to Visit 1 or during the study (unless otherwise specified):

Medication No use within the following time intervals prior to Screening or thereafter at any time during the study (unless otherwise specified) Inhaled Long acting beta-agonists (LABA) 48 hours ICS/LABA combination products 48 hours Inhaled corticosteroids 48 hours Tiotropium 1 week Systemic, Oral, parenteral, intra-articular corticosteroids 30 days (oral and systemic corticosteroids may be used to treat COPD exacerbations during the study) Cytochrome P450 3A4 strong inhibitors including but not limited to antiretrovirals (protease inhibitors) (e.g.Indinavir, Nelfinavir, Ritonavir, Saquinavir); Imidazole and Triazole anti-fungals (e.g. Ketaconazole, Itraconazole); Clarithromycin, Telithromycin, Amiodarone, and Nefazodone 6 weeks Grapefruit is allowed up to Visit 1, then limited to no more than one glass of grapefruit juice (250 mL/ 8 ounces) or one grapefruit per day Any other investigational drug 30 days or 5 half lives whichever is longer.

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Chronic Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• fluticasone furoate/vilanterol
100/25mcg given once daily via novel dry powder inhaler
• fluticasone furoate
100mcg given once daily via novel dry powder inhaler
• vilanterol
25mcg given once daily via novel dry powder inhaler

Other:
• Placebo
placebo comparator once daily via novel dry powder inhaler

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Adrogue	Buenos Aires
Argentina	GSK Investigational Site	Bahia Blanca	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Cipoletti, Rio Negro	Río Negro
Argentina	GSK Investigational Site	Ciudad Autnónoma de Buenos Aires	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 Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Concepcion del Uruguay	Entre Ríos
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Cordoba	Córdova
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Cordoba
Argentina	GSK Investigational Site	Coronel Suarez
Argentina	GSK Investigational Site	Corrientes
Argentina	GSK Investigational Site	Derqui, Pilar	Buenos Aires
Argentina	GSK Investigational Site	Florencio Varela	Buenos Aires
Argentina	GSK Investigational Site	Florencio Varela
Argentina	GSK Investigational Site	Formosa
Argentina	GSK Investigational Site	Godoy Cruz	Mendoza
Argentina	GSK Investigational Site	Jujuy
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	La Plata	Buenos Aires
Argentina	GSK Investigational Site	Lanús
Argentina	GSK Investigational Site	Mar del Plata
Argentina	GSK Investigational Site	Mar del Plata	Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Monte Grande
Argentina	GSK Investigational Site	Nueve de Julio	Buenos Aires
Argentina	GSK Investigational Site	Olivos	Buenos Aires
Argentina	GSK Investigational Site	Parana	Entre Ríos
Argentina	GSK Investigational Site	Pergamino	Buenos Aires
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
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	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario
Argentina	GSK Investigational Site	Rosario
Argentina	GSK Investigational Site	Salta
Argentina	GSK Investigational Site	Salta
Argentina	GSK Investigational Site	San Isidro	Buenos Aires
Argentina	GSK Investigational Site	San Luis
Argentina	GSK Investigational Site	San Martin	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucuman
Argentina	GSK Investigational Site	San Miguel de Tucumán
Argentina	GSK Investigational Site	San Nicolas	Buenos Aires
Argentina	GSK Investigational Site	San Nicolas	Buenos Aires
Argentina	GSK Investigational Site	Santa Fe
Argentina	GSK Investigational Site	Santa Fe
Argentina	GSK Investigational Site	Santiago del Estero
Argentina	GSK Investigational Site	Tucuman	Tucumán
Argentina	GSK Investigational Site	Vicente López	Buenos Aires
Australia	GSK Investigational Site	Bedford Park	South Australia
Australia	GSK Investigational Site	Cairns	Queensland
Australia	GSK Investigational Site	Daw Park	South Australia
Australia	GSK Investigational Site	Footscray	Victoria
Australia	GSK Investigational Site	Geelong	Victoria
Australia	GSK Investigational Site	Glen Osmond
Australia	GSK Investigational Site	Melbourne	Victoria
Australia	GSK Investigational Site	Redcliffe	Queensland
Austria	GSK Investigational Site	Feldbach
Austria	GSK Investigational Site	Feldkirch
Austria	GSK Investigational Site	Grieskirchen
Austria	GSK Investigational Site	Innsbruck
Austria	GSK Investigational Site	Linz
Austria	GSK Investigational Site	Salzburg
Austria	GSK Investigational Site	Salzburg
Austria	GSK Investigational Site	Spittal/Drau
Austria	GSK Investigational Site	Thalheim bei Wels
Austria	GSK Investigational Site	Vienna
Austria	GSK Investigational Site	Wels
Austria	GSK Investigational Site	Zwettl
Belarus	GSK Investigational Site	Brest
Belarus	GSK Investigational Site	Gomel
Belarus	GSK Investigational Site	Grodno
Belarus	GSK Investigational Site	Minsk
Belarus	GSK Investigational Site	Minsk
Belarus	GSK Investigational Site	Minsk
Belarus	GSK Investigational Site	Vitebsk
Belgium	GSK Investigational Site	Diest
Belgium	GSK Investigational Site	Erpent
Belgium	GSK Investigational Site	Gilly
Belgium	GSK Investigational Site	Mons
Belgium	GSK Investigational Site	Namur
Bosnia and Herzegovina	GSK Investigational Site	Banja Luka
Bosnia and Herzegovina	GSK Investigational Site	Banjaluka
Bosnia and Herzegovina	GSK Investigational Site	Bihac
Bosnia and Herzegovina	GSK Investigational Site	Bihac
Bosnia and Herzegovina	GSK Investigational Site	Bijeljina
Bosnia and Herzegovina	GSK Investigational Site	Brcko
Bosnia and Herzegovina	GSK Investigational Site	Foca
Bosnia and Herzegovina	GSK Investigational Site	Gracanica
Bosnia and Herzegovina	GSK Investigational Site	Gradiska
Bosnia and Herzegovina	GSK Investigational Site	Istocno Sarajevo
Bosnia and Herzegovina	GSK Investigational Site	Konjic
Bosnia and Herzegovina	GSK Investigational Site	Mostar
Bosnia and Herzegovina	GSK Investigational Site	Novi Travnik
Bosnia and Herzegovina	GSK Investigational Site	Pale
Bosnia and Herzegovina	GSK Investigational Site	Sarajevo
Bosnia and Herzegovina	GSK Investigational Site	Sarajevo
Bosnia and Herzegovina	GSK Investigational Site	Srebrenik
Bosnia and Herzegovina	GSK Investigational Site	Tesanj
Bosnia and Herzegovina	GSK Investigational Site	Teslic
Bosnia and Herzegovina	GSK Investigational Site	Travnik
Bosnia and Herzegovina	GSK Investigational Site	Trebinje
Bosnia and Herzegovina	GSK Investigational Site	Tuzla
Bosnia and Herzegovina	GSK Investigational Site	Visegrad
Bosnia and Herzegovina	GSK Investigational Site	Zenica
Bulgaria	GSK Investigational Site	Blagoevgrad
Bulgaria	GSK Investigational Site	Dimitrovgrad
Bulgaria	GSK Investigational Site	Gabrovo
Bulgaria	GSK Investigational Site	Kozlodui
Bulgaria	GSK Investigational Site	Lovech
Bulgaria	GSK Investigational Site	Pazardjik
Bulgaria	GSK Investigational Site	Petrich
Bulgaria	GSK Investigational Site	Pleven
Bulgaria	GSK Investigational Site	Plovdiv
Bulgaria	GSK Investigational Site	Razgrad
Bulgaria	GSK Investigational Site	Rousse
Bulgaria	GSK Investigational Site	Sevlievo
Bulgaria	GSK Investigational Site	Sliven
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Sofia
Bulgaria	GSK Investigational Site	Stara Zagora
Bulgaria	GSK Investigational Site	Stara Zagora
Bulgaria	GSK Investigational Site	Troyan
Bulgaria	GSK Investigational Site	Varna
Bulgaria	GSK Investigational Site	Veliko Tarnovo
Bulgaria	GSK Investigational Site	Vidin
Canada	GSK Investigational Site	Bolton	Ontario
Canada	GSK Investigational Site	Burlington	Ontario
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Edmonton	Alberta
Canada	GSK Investigational Site	Grimsby	Ontario
Canada	GSK Investigational Site	Kamloops	British Columbia
Canada	GSK Investigational Site	London	Ontario
Canada	GSK Investigational Site	Mirabel	Quebec
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Mississauga	Ontario
Canada	GSK Investigational Site	Montreal	Quebec
Canada	GSK Investigational Site	Newmarket	Ontario
Canada	GSK Investigational Site	Orleans	Ontario
Canada	GSK Investigational Site	Penticton	British Columbia
Canada	GSK Investigational Site	Quebec
Canada	GSK Investigational Site	Sainte Jerome	Quebec
Canada	GSK Investigational Site	Sarnia	Ontario
Canada	GSK Investigational Site	Toronto	Ontario
Canada	GSK Investigational Site	Vancouver	British Columbia
Canada	GSK Investigational Site	West Vancouver	British Columbia
Canada	GSK Investigational Site	Windsor	Ontario
Canada	GSK Investigational Site	Winnipeg	Manitoba
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Chile	GSK Investigational Site	Temuco	Región De La Araucania
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
China	GSK Investigational Site	Baotou	Inner Mongolia
China	GSK Investigational Site	Baotou
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	Bengbu
China	GSK Investigational Site	Changchun
China	GSK Investigational Site	Chengdu
China	GSK Investigational Site	Chengdu	Sichuan
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Chongqing
China	GSK Investigational Site	Fu Zhou
China	GSK Investigational Site	Fuzhou
China	GSK Investigational Site	Guangxi
China	GSK Investigational Site	Guangzhou
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	Haikou	Hainan
China	GSK Investigational Site	Hangzhou
China	GSK Investigational Site	Hefei
China	GSK Investigational Site	Hohhot	Hainan
China	GSK Investigational Site	Huai'an
China	GSK Investigational Site	Jiangyin
China	GSK Investigational Site	Jinan	Shandong
China	GSK Investigational Site	Luzhou
China	GSK Investigational Site	Nanchang
China	GSK Investigational Site	Nanjing
China	GSK Investigational Site	Nanning	Guangxi
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	ShangHai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shanghai
China	GSK Investigational Site	Shenyang	Liaoning
China	GSK Investigational Site	Shenzhen	Guangdong
China	GSK Investigational Site	Shijiazhuang	Hebei
China	GSK Investigational Site	Taiyuan	Shanxi
China	GSK Investigational Site	Tianjin
China	GSK Investigational Site	Wuhan	Hubei
China	GSK Investigational Site	Wuxi
China	GSK Investigational Site	Xian	Shaanxi
China	GSK Investigational Site	Yinchuan	Ningxia
China	GSK Investigational Site	Zhanjiang	Guangdong
Colombia	GSK Investigational Site	Barranquilla
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Bogota
Colombia	GSK Investigational Site	Bogotá
Colombia	GSK Investigational Site	Bogotá
Colombia	GSK Investigational Site	Cali
Colombia	GSK Investigational Site	Medellin
Colombia	GSK Investigational Site	Medellin
Colombia	GSK Investigational Site	Zipaquira
Croatia	GSK Investigational Site	Cakovec
Croatia	GSK Investigational Site	Draganic
Croatia	GSK Investigational Site	Hrasce Turopoljsko
Croatia	GSK Investigational Site	Hreljin
Croatia	GSK Investigational Site	Ivankovo
Croatia	GSK Investigational Site	Karlovac
Croatia	GSK Investigational Site	Klenovnik
Croatia	GSK Investigational Site	Krapina
Croatia	GSK Investigational Site	Kutina
Croatia	GSK Investigational Site	Novi Marof
Croatia	GSK Investigational Site	Osijek
Croatia	GSK Investigational Site	Retkovci
Croatia	GSK Investigational Site	Rijeka
Croatia	GSK Investigational Site	Samobor
Croatia	GSK Investigational Site	Senj
Croatia	GSK Investigational Site	Sibenik
Croatia	GSK Investigational Site	Sisak
Croatia	GSK Investigational Site	Split
Croatia	GSK Investigational Site	Strmec Samoborski
Croatia	GSK Investigational Site	Stubicke toplice
Croatia	GSK Investigational Site	Sukosan
Croatia	GSK Investigational Site	Varazdin
Croatia	GSK Investigational Site	Zabok
Croatia	GSK Investigational Site	Zadar
Croatia	GSK Investigational Site	Zagreb
Czechia	GSK Investigational Site	Benesov
Czechia	GSK Investigational Site	Beroun
Czechia	GSK Investigational Site	Brno
Czechia	GSK Investigational Site	Havlickuv brod
Czechia	GSK Investigational Site	Hlucin
Czechia	GSK Investigational Site	Holesov
Czechia	GSK Investigational Site	Jaromer
Czechia	GSK Investigational Site	Jindrichuv Hradec
Czechia	GSK Investigational Site	Kolin
Czechia	GSK Investigational Site	Kralupy nad Vltavou
Czechia	GSK Investigational Site	Kromeriz
Czechia	GSK Investigational Site	Liberec
Czechia	GSK Investigational Site	Melnik
Czechia	GSK Investigational Site	Moravsky Krumlov
Czechia	GSK Investigational Site	Neratovice
Czechia	GSK Investigational Site	Novy Jicin
Czechia	GSK Investigational Site	Ostrava
Czechia	GSK Investigational Site	Ostrava - Belsky les
Czechia	GSK Investigational Site	Ostrava - Poruba
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Plzen
Czechia	GSK Investigational Site	Praha 1
Czechia	GSK Investigational Site	Praha 13
Czechia	GSK Investigational Site	Praha 17
Czechia	GSK Investigational Site	Praha 3
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Praha 4
Czechia	GSK Investigational Site	Praha 5
Czechia	GSK Investigational Site	Praha 6
Czechia	GSK Investigational Site	Rokycany
Czechia	GSK Investigational Site	Rudna
Czechia	GSK Investigational Site	Strakonice
Czechia	GSK Investigational Site	Strakonice
Czechia	GSK Investigational Site	Svitavy
Czechia	GSK Investigational Site	Tremosna
Czechia	GSK Investigational Site	Usti Nad Labem - Klise
Czechia	GSK Investigational Site	Zatec
France	GSK Investigational Site	Ferolles Attilly
France	GSK Investigational Site	Paris Cedex 04
France	GSK Investigational Site	Strasbourg Cedex
France	GSK Investigational Site	Tarbes
France	GSK Investigational Site	Toulouse cedex 9
Georgia	GSK Investigational Site	Batumi
Georgia	GSK Investigational Site	Gurjaani
Georgia	GSK Investigational Site	Kutaisi
Georgia	GSK Investigational Site	Kvemo Kartli
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Georgia	GSK Investigational Site	Tbilisi
Germany	GSK Investigational Site	Aschaffenburg	Bayern
Germany	GSK Investigational Site	Augsburg	Bayern
Germany	GSK Investigational Site	Augsburg	Bayern
Germany	GSK Investigational Site	Bad Woerrishofen	Bayern
Germany	GSK Investigational Site	Bensheim	Hessen
Germany	GSK Investigational Site	Bergisch Gladbach	Nordrhein-Westfalen
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	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	Bochum	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bonn	Nordrhein-Westfalen
Germany	GSK Investigational Site	Bruchsal	Baden-Wuerttemberg
Germany	GSK Investigational Site	Cottbus	Brandenburg
Germany	GSK Investigational Site	Darmstadt	Hessen
Germany	GSK Investigational Site	Deggingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Dortmund	Nordrhein-Westfalen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dresden	Sachsen
Germany	GSK Investigational Site	Dueren	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Essen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Ettlingen	Baden-Wuerttemberg
Germany	GSK Investigational Site	Feldkirchen	Bayern
Germany	GSK Investigational Site	Foehren	Rheinland-Pfalz
Germany	GSK Investigational Site	Frankfurt	Baden-Wuerttemberg
Germany	GSK Investigational Site	Fuerth	Bayern
Germany	GSK Investigational Site	Gauting	Bayern
Germany	GSK Investigational Site	Gelsenkirchen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Goerlitz	Sachsen
Germany	GSK Investigational Site	Goettingen	Niedersachsen
Germany	GSK Investigational Site	Hagen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hagen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hamburg
Germany	GSK Investigational Site	Hannover	Niedersachsen
Germany	GSK Investigational Site	Harsewinkel	Nordrhein-Westfalen
Germany	GSK Investigational Site	Hoechstadt	Bayern
Germany	GSK Investigational Site	Ingelheim	Rheinland-Pfalz
Germany	GSK Investigational Site	Jena	Thueringen
Germany	GSK Investigational Site	Karlsruhe	Baden-Wuerttemberg
Germany	GSK Investigational Site	Kassel	Hessen
Germany	GSK Investigational Site	Koeln	Nordrhein-Westfalen
Germany	GSK Investigational Site	Landsberg	Bayern
Germany	GSK Investigational Site	Leipzg	Sachsen
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	Magdeburg	Sachsen-Anhalt
Germany	GSK Investigational Site	Mainz	Rheinland-Pfalz
Germany	GSK Investigational Site	Marburg	Hessen
Germany	GSK Investigational Site	Muenchen	Bayern
Germany	GSK Investigational Site	München
Germany	GSK Investigational Site	Neuss	Nordrhein-Westfalen
Germany	GSK Investigational Site	Neuwied	Rheinland-Pfalz
Germany	GSK Investigational Site	Papenburg	Niedersachsen
Germany	GSK Investigational Site	Potsdam	Brandenburg
Germany	GSK Investigational Site	Reinfeld	Schleswig-Holstein
Germany	GSK Investigational Site	Rhaunen	Rheinland-Pfalz
Germany	GSK Investigational Site	Riesa	Sachsen
Germany	GSK Investigational Site	Ruedersdorf	Brandenburg
Germany	GSK Investigational Site	Schleswig	Schleswig-Holstein
Germany	GSK Investigational Site	Solingen	Nordrhein-Westfalen
Germany	GSK Investigational Site	Stuhr	Niedersachsen
Germany	GSK Investigational Site	Vilshofen	Bayern
Germany	GSK Investigational Site	Wardenburg	Niedersachsen
Germany	GSK Investigational Site	Weissenhorn	Bayern
Germany	GSK Investigational Site	Zerbst	Sachsen-Anhalt
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Thessaloniki
Hungary	GSK Investigational Site	Balassagyarmat
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
Hungary	GSK Investigational Site	Budapest
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	Kaposvár
Hungary	GSK Investigational Site	Komarom
Hungary	GSK Investigational Site	Komló
Hungary	GSK Investigational Site	Mosonmagyaróvár
Hungary	GSK Investigational Site	Nagykanizsa
Hungary	GSK Investigational Site	Nyiregyhaza
Hungary	GSK Investigational Site	Pécs
Hungary	GSK Investigational Site	Sopron
Hungary	GSK Investigational Site	Szigetszentmiklos
Hungary	GSK Investigational Site	Szikszó
Hungary	GSK Investigational Site	Szombathely
Hungary	GSK Investigational Site	Tatabanya
Hungary	GSK Investigational Site	Vasarosnameny
Hungary	GSK Investigational Site	Zalaegerszeg
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Ahmedabad
India	GSK Investigational Site	Alappuzha
India	GSK Investigational Site	Angamaly
India	GSK Investigational Site	Aurangabad
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Bangalore
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Chennai
India	GSK Investigational Site	Guntur
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Hyderabad
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Jaipur
India	GSK Investigational Site	Lucknow
India	GSK Investigational Site	Mysore
India	GSK Investigational Site	Mysore
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	Nashik
India	GSK Investigational Site	Nasik
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Pune
India	GSK Investigational Site	Trisshur
India	GSK Investigational Site	Trivandrum
India	GSK Investigational Site	Varanasi
India	GSK Investigational Site	Varanasi
India	GSK Investigational Site	Vijayawada
Indonesia	GSK Investigational Site	Banda Aceh
Indonesia	GSK Investigational Site	Banjarmasin
Indonesia	GSK Investigational Site	Bukittinggi
Indonesia	GSK Investigational Site	Denpasar
Indonesia	GSK Investigational Site	Depok Timur
Indonesia	GSK Investigational Site	Jakarta
Indonesia	GSK Investigational Site	Jakarta
Indonesia	GSK Investigational Site	Jakarta
Indonesia	GSK Investigational Site	Lampung Selatan
Indonesia	GSK Investigational Site	Makassar
Indonesia	GSK Investigational Site	Malang
Indonesia	GSK Investigational Site	Medan
Indonesia	GSK Investigational Site	Medan
Indonesia	GSK Investigational Site	Padang
Indonesia	GSK Investigational Site	Palembang
Indonesia	GSK Investigational Site	Pekanbaru
Indonesia	GSK Investigational Site	Pontianak
Indonesia	GSK Investigational Site	Pringsewu
Indonesia	GSK Investigational Site	Semarang
Indonesia	GSK Investigational Site	Surabaya
Indonesia	GSK Investigational Site	Surakarta
Indonesia	GSK Investigational Site	Yogyakarta
Israel	GSK Investigational Site	Afula
Israel	GSK Investigational Site	Ashkelon
Israel	GSK Investigational Site	Beer-Sheba
Israel	GSK Investigational Site	Hadera
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Haifa
Israel	GSK Investigational Site	Holon
Israel	GSK Investigational Site	Jerusalem
Israel	GSK Investigational Site	Kfar Saba
Israel	GSK Investigational Site	Rehovot
Israel	GSK Investigational Site	Tel Aviv
Israel	GSK Investigational Site	Tel Hashomer
Italy	GSK Investigational Site	Pordenone	Friuli-Venezia-Giulia
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Aichi
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hokkaido
Japan	GSK Investigational Site	Hyogo
Japan	GSK Investigational Site	Ibaraki
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kodaira
Japan	GSK Investigational Site	Kumamoto
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Oita
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Japan	GSK Investigational Site	Tokyo
Korea, Republic of	GSK Investigational Site	Bucheon
Korea, Republic of	GSK Investigational Site	Bucheon-Si, Gyeonggi-Do
Korea, Republic of	GSK Investigational Site	Busan
Korea, Republic of	GSK Investigational Site	Cheonan
Korea, Republic of	GSK Investigational Site	Chonju-si
Korea, Republic of	GSK Investigational Site	Daegu
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Daejeon
Korea, Republic of	GSK Investigational Site	Goyang-si
Korea, Republic of	GSK Investigational Site	Guri-si
Korea, Republic of	GSK Investigational Site	Gwangju
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Kangwon
Korea, Republic of	GSK Investigational Site	Seongnam
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
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
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	Suwon, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Uijeongbu, Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Ulsan
Korea, Republic of	GSK Investigational Site	Wonju-si, Kanwon-do
Latvia	GSK Investigational Site	Balvi
Latvia	GSK Investigational Site	Daugavpils
Latvia	GSK Investigational Site	Daugavpils
Latvia	GSK Investigational Site	Jekabpils
Latvia	GSK Investigational Site	Jelgava
Latvia	GSK Investigational Site	Jurmala
Latvia	GSK Investigational Site	Kraslava
Latvia	GSK Investigational Site	Kuldiga
Latvia	GSK Investigational Site	Liepaja
Latvia	GSK Investigational Site	Ogre
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Riga
Latvia	GSK Investigational Site	Talsi
Latvia	GSK Investigational Site	Tukums
Latvia	GSK Investigational Site	Valmiera
Latvia	GSK Investigational Site	Ventspils
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Bitola
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Gostivar
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Ohrid
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Prilep
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Shtip
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Skopje
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Strumica
Macedonia, The Former Yugoslav Republic of	GSK Investigational Site	Veles
Malaysia	GSK Investigational Site	Johor Bahru
Malaysia	GSK Investigational Site	Kuala Lumpur
Malaysia	GSK Investigational Site	Kuala Pilah
Malaysia	GSK Investigational Site	Kuching
Malaysia	GSK Investigational Site	Selangor
Malaysia	GSK Investigational Site	Sibu
Malaysia	GSK Investigational Site	Sungai Petani, Kedah
Malaysia	GSK Investigational Site	Taiping Perak
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Chihuahua
Mexico	GSK Investigational Site	Cuautitlan Izcalli	Estado De México
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Guadalajara
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Hermosillo	Sonora
Mexico	GSK Investigational Site	Hidalgo
Mexico	GSK Investigational Site	Merida
Mexico	GSK Investigational Site	Mexico D.F
Mexico	GSK Investigational Site	México DF
Mexico	GSK Investigational Site	Monterrey
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Monterrey	Nuevo León
Mexico	GSK Investigational Site	Morelia	Michoacán
Mexico	GSK Investigational Site	San luis Potosí
Mexico	GSK Investigational Site	Zapopan	Jalisco
Netherlands	GSK Investigational Site	Alkmaar
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Ede Gld
Netherlands	GSK Investigational Site	Helmond
Netherlands	GSK Investigational Site	Zutphen
Philippines	GSK Investigational Site	Alabang, Muntinlupa City
Philippines	GSK Investigational Site	Caloocan
Philippines	GSK Investigational Site	Cavite
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Dasmariñas, Cavite
Philippines	GSK Investigational Site	Davao
Philippines	GSK Investigational Site	Iloilo
Philippines	GSK Investigational Site	Iloilo City
Philippines	GSK Investigational Site	Jaro, Iloilo City
Philippines	GSK Investigational Site	Los Banos
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Marilao, Bulacan
Philippines	GSK Investigational Site	Pasay
Philippines	GSK Investigational Site	Pasig
Philippines	GSK Investigational Site	Quezon
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	Quezon City
Philippines	GSK Investigational Site	San Fernando, Pampanga
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bialystok
Poland	GSK Investigational Site	Bielsko-Biala
Poland	GSK Investigational Site	Bielsko-Biala
Poland	GSK Investigational Site	Bienkowka
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Bydgoszcz
Poland	GSK Investigational Site	Chelmza
Poland	GSK Investigational Site	Chodziez
Poland	GSK Investigational Site	Chorzow
Poland	GSK Investigational Site	Choszczno
Poland	GSK Investigational Site	Czestochowa
Poland	GSK Investigational Site	Dabrowa Gornicza
Poland	GSK Investigational Site	Dzialdowo
Poland	GSK Investigational Site	Elblag
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdansk
Poland	GSK Investigational Site	Gdynia
Poland	GSK Investigational Site	Gorzow Wielkopolski
Poland	GSK Investigational Site	Grudziadz
Poland	GSK Investigational Site	Ilawa
Poland	GSK Investigational Site	Inowroclaw
Poland	GSK Investigational Site	Izabelin
Poland	GSK Investigational Site	Jelenia Gora
Poland	GSK Investigational Site	Karpacz
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Katowice
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Kielce
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krakow
Poland	GSK Investigational Site	Krotoszyn
Poland	GSK Investigational Site	Ksawerow
Poland	GSK Investigational Site	Kutno
Poland	GSK Investigational Site	Leczyca
Poland	GSK Investigational Site	Libiaz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Lublin
Poland	GSK Investigational Site	Olawa
Poland	GSK Investigational Site	Olsztyn
Poland	GSK Investigational Site	Ostrow Wilekopolski
Poland	GSK Investigational Site	Ostrowiec Swietokrzyski
Poland	GSK Investigational Site	Piaseczno
Poland	GSK Investigational Site	Pila
Poland	GSK Investigational Site	Plock
Poland	GSK Investigational Site	Police
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Ruda Slaska
Poland	GSK Investigational Site	Rudka
Poland	GSK Investigational Site	Rzeszow
Poland	GSK Investigational Site	Skarzysko-Kamienna
Poland	GSK Investigational Site	Skierniewice
Poland	GSK Investigational Site	Slupsk
Poland	GSK Investigational Site	Sopot
Poland	GSK Investigational Site	Swidnik
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Szczecin
Poland	GSK Investigational Site	Tarnow
Poland	GSK Investigational Site	Tczew
Poland	GSK Investigational Site	Torun
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Warszawa
Poland	GSK Investigational Site	Wloclawek
Poland	GSK Investigational Site	Wloszczowa
Poland	GSK Investigational Site	Wodzislaw Slaski
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Wroclaw
Poland	GSK Investigational Site	Zabrze
Poland	GSK Investigational Site	Zabrze
Poland	GSK Investigational Site	Zgierz
Romania	GSK Investigational Site	Arad
Romania	GSK Investigational Site	Bacau
Romania	GSK Investigational Site	Bragadiru
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Brasov
Romania	GSK Investigational Site	Bucarest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Bucuresti
Romania	GSK Investigational Site	Campulung Muscel
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Cluj-Napoca
Romania	GSK Investigational Site	Codlea
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Constanta
Romania	GSK Investigational Site	Deva
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Iasi
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Pitesti
Romania	GSK Investigational Site	Ploiesti
Romania	GSK Investigational Site	Ramnicu Valcea
Romania	GSK Investigational Site	Suceava
Romania	GSK Investigational Site	Targu-Mures
Romania	GSK Investigational Site	Timisoara
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Arkhangelsk
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Barnaul
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Ekaterinburg
Russian Federation	GSK Investigational Site	Gatchina
Russian Federation	GSK Investigational Site	Ivanovo
Russian Federation	GSK Investigational Site	Izhevsk
Russian Federation	GSK Investigational Site	Kaliningrad
Russian Federation	GSK Investigational Site	Kazan
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kemerovo
Russian Federation	GSK Investigational Site	Kirov
Russian Federation	GSK Investigational Site	Krasnoyarsk
Russian Federation	GSK Investigational Site	Kursk
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Moscow
Russian Federation	GSK Investigational Site	Nizhniy Novgorod
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Novosibirsk
Russian Federation	GSK Investigational Site	Orenburg
Russian Federation	GSK Investigational Site	Orenburg
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	Perm
Russian Federation	GSK Investigational Site	Pskov
Russian Federation	GSK Investigational Site	Rostov-on-Don
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Ryazan
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Saratov
Russian Federation	GSK Investigational Site	Sestroretsk
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	Smolensk
Russian Federation	GSK Investigational Site	St Petersburg
Russian Federation	GSK Investigational Site	St Petersburg
Russian Federation	GSK Investigational Site	St'Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St-Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St. Petersburg
Russian Federation	GSK Investigational Site	St.?etersburg
Russian Federation	GSK Investigational Site	St.Petersburg
Russian Federation	GSK Investigational Site	St.Petersburg
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tomsk
Russian Federation	GSK Investigational Site	Tver
Russian Federation	GSK Investigational Site	Ufa
Russian Federation	GSK Investigational Site	Ulyanovsk
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Voronezh
Russian Federation	GSK Investigational Site	Vsevolzhsk
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Russian Federation	GSK Investigational Site	Yaroslavl
Serbia	GSK Investigational Site	Belgrade
Serbia	GSK Investigational Site	Belgrade
Serbia	GSK Investigational Site	Cacak
Serbia	GSK Investigational Site	Kragujevac
Serbia	GSK Investigational Site	Nis
Serbia	GSK Investigational Site	Sombor
Serbia	GSK Investigational Site	Sremska Kamenica
Serbia	GSK Investigational Site	Valjevo
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Bratislava
Slovakia	GSK Investigational Site	Kosice
Slovakia	GSK Investigational Site	Kralovsky Chlmec
Slovakia	GSK Investigational Site	Nove Zamky
Slovakia	GSK Investigational Site	Presov
Slovakia	GSK Investigational Site	Presov
Slovakia	GSK Investigational Site	Spisska Nova Ves
Slovakia	GSK Investigational Site	Sturovo
Slovakia	GSK Investigational Site	Trnava
Slovakia	GSK Investigational Site	Vrable
South Africa	GSK Investigational Site	Benoni	Gauteng
South Africa	GSK Investigational Site	Benoni
South Africa	GSK Investigational Site	Bloemfontein
South Africa	GSK Investigational Site	Boksburg	Gauteng
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	Cape Town
South Africa	GSK Investigational Site	CapeTown
South Africa	GSK Investigational Site	Dundee	KwaZulu- Natal
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Durban
South Africa	GSK Investigational Site	Gatesville
South Africa	GSK Investigational Site	Johannesburg
South Africa	GSK Investigational Site	Korsten
South Africa	GSK Investigational Site	Lynnwood Ridge
South Africa	GSK Investigational Site	Meyerspark	Gauteng
South Africa	GSK Investigational Site	Middelburg	Mpumalanga
South Africa	GSK Investigational Site	Morningside	Gauteng
South Africa	GSK Investigational Site	Mowbray
South Africa	GSK Investigational Site	Paarl
South Africa	GSK Investigational Site	Panorama
South Africa	GSK Investigational Site	Potchefstroom
South Africa	GSK Investigational Site	Pretoria
South Africa	GSK Investigational Site	Pretoria
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Pretoria	Gauteng
South Africa	GSK Investigational Site	Roodepoort
South Africa	GSK Investigational Site	Rooihuiskraal
South Africa	GSK Investigational Site	Somerset West
South Africa	GSK Investigational Site	Thaba Tshwane	Gauteng
South Africa	GSK Investigational Site	Thabazimbi
South Africa	GSK Investigational Site	Tygerberg
South Africa	GSK Investigational Site	Voorspoed
Spain	GSK Investigational Site	Badalona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Benidorm
Spain	GSK Investigational Site	Canet De Mar - Barcelona
Spain	GSK Investigational Site	Galdakano
Spain	GSK Investigational Site	Illescas-Toledo
Spain	GSK Investigational Site	Jerez de la Frontera
Spain	GSK Investigational Site	L'Hospitalet de Llobregat
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Mataró
Spain	GSK Investigational Site	Oviedo
Spain	GSK Investigational Site	Palma de Mallorca
Spain	GSK Investigational Site	Pamplona
Spain	GSK Investigational Site	Pozuelo De Alarcón/Madrid
Spain	GSK Investigational Site	Sabadell (Barcelona)
Spain	GSK Investigational Site	Sagunto/Valencia
Spain	GSK Investigational Site	Sant Boi de Llobregat
Spain	GSK Investigational Site	Santa Coloma de Gramenet
Spain	GSK Investigational Site	Santiago de Compostela
Spain	GSK Investigational Site	Torrelavega
Spain	GSK Investigational Site	Valencia
Spain	GSK Investigational Site	Vic (Barcelona)
Taiwan	GSK Investigational Site	Changhua
Taiwan	GSK Investigational Site	Chia-Yi
Taiwan	GSK Investigational Site	Kaohsiung
Taiwan	GSK Investigational Site	Kaohsiung Hsien
Taiwan	GSK Investigational Site	Keelung
Taiwan	GSK Investigational Site	LinKou
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Taichung
Taiwan	GSK Investigational Site	Tainan
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Taipei
Taiwan	GSK Investigational Site	Yung Kang City
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Bangkok
Thailand	GSK Investigational Site	Chiangmai
Thailand	GSK Investigational Site	Chiangrai
Thailand	GSK Investigational Site	Khon Kaen
Thailand	GSK Investigational Site	Mae Rim, Chiang Mai
* Note: There are 1621 locations in all - only the first 1000 are shown.

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Vietnam,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Croatia,  Czechia,  France,  Georgia,  Germany,  Greece,  Hungary,  India,  Indonesia,  Israel,  Italy,  Japan,  Korea, Republic of,  Latvia,  Macedonia, The Former Yugoslav Republic of,  Malaysia,  Mexico,  Netherlands,  Philippines,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  South Africa,  Spain,  Taiwan,  Thailand,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Death (Both on and Off Treatment) Due to Any Cause, Time up to or on the Pre-determined Common End Date	Death from any cause: which occurred from the day of starting IP until the Commone End Date (CED). Common End Date (CED) is the study end date that was pre determined where approximately 1000 deaths would have occurred in the Intent-toTreat Efficacy (ITT-E) Population. Only deaths which occurred on or before the CED were used for the primary analysis. Those who had not died by CED, but who were known to be alive on or after the CED, were censored at the CED. Cox Proportional Hazards (PH) Model was adjusted for age, and gender, including all 4 arms. A hazard ratio of less than 1 indicates a lower death rate versus placebo or other arm. ITT-E Population consisted of all participants in the Safety Population (i.e. randomized to IP and who received at least one dose of IP), with the exception of those recruited at sites that were closed.	From the date of randomization until date of death due to any cause (average of 2 study years)
Secondary	Decline in Forced Expiratory Volume in 1 Second (FEV1)	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. The effect of treatment on decline of post bronchodilator FEV1 recorded during the treatment period was analyzed using a particular form of a mixed effect model - a random coefficients model. FEV1 was fitted as the response variable with treatment group, age, gender, baseline FEV1 and time on treatment as fixed effects. Time on treatment was treated as a continuous variable. This model allowed for an initial increase in FEV1, but then tested the difference in slopes from the first post-baseline measurement which was at 3 months. A negative slope indicates a decline. A positive treatment difference indicates a slower rate of decline vs Placebo or Component. Only participants with at least one on-treatment post-bronchodilator FEV1 measurement were analyzed.	From start date of IP until IP stop date + 1 (assessed up to 4 years)
Secondary	Number of Participants With First On-treatment Cardiovascular (CV) Composite Events Occured on or Before Common End Date	On-treatment CV composite event is comprised of the first event that is adjudicated as on-treatment CV death, myocardial infarction, stroke, unstable angina, or transient ischemic attack experienced by a participant. The events that occurred no more than 7 days after the participants last dose of IP are considered as on-treatment adverse events. Common end date is the study end date where approximately 1000 deaths would have occurred in the ITT-E Population. Cox PH Model was used to assess time to first on-treatment CV composite event. Cox PH Model was adjusted for age, gender and indicators of ischemic and vascular disease, including all four treatment arms. A hazard ratio less than 1 indicates a lower risk of a first CV event rate versus placebo or any arm.	From the start of IP to first on treatment CV event till 7 days after the last dose of IP (average of 2 study years)

External Links

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