QVA vs. Salmeterol/Fluticasone, 52-week Exacerbation Study, FLAME (EFfect of Indacaterol Glycopyronium Vs Fluticasone Salmeterol on COPD Exacerbations)

A 52-week Treatment, Multi-center, Randomized, Double-blind, Double Dummy, Parallel-group, Active Controlled Study to Compare the Effect of QVA149 (Indacaterol Maleate / Glycopyrronium Bromide) With Salmeterol/Fluticasone on the Rate of Exacerbations in Subjects With Moderate to Very Severe COPD. (FLAME).

This study will assess the efficacy, safety and tolerability of QVA149 in patients with moderate to very severe COPD.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Drug: QVA149; Drug: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS)

• Study Type: Interventional
• Enrollment (Actual): 3362
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1120AAC
    • Novartis Investigative Site
  • Buenos Aires, Argentina, 1425
    • Novartis Investigative Site
  • Ciudad de Buenos Aires, Argentina, C1425AUA
    • Novartis Investigative Site
  • Mendoza, Argentina, 5500
    • Novartis Investigative Site
  • Mendoza, Argentina, M5500CBA
    • Novartis Investigative Site
  • Salta, Argentina, 4000
    • Novartis Investigative Site
  • Santa Fe, Argentina, S3000FIL
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1056ABJ
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1122AAK
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1426ABP
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1425BEN
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, 1122
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1414AIF
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    • Caba, Buenos Aires, Argentina, C1424BSF
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1425BEA
      • Novartis Investigative Site
    • Lanus, Buenos Aires, Argentina, B8000XAV
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, B7600FZN
      • Novartis Investigative Site
    • Mar del Plata, Buenos Aires, Argentina, 7600
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    • Mar del Plata, Buenos Aires, Argentina, B7600
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  • Capital Federal
    • Buenos Aires, Capital Federal, Argentina, C1028AAP
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  • Entre Ríos
    • Concepcion del Uruguay, Entre Ríos, Argentina, 3260
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  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DBS
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    • Rosario, Santa Fe, Argentina, S2000AII
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  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, 4000
      • Novartis Investigative Site
    • San Miguel de Tucuman, Tucuman, Argentina, T4000IFL
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• Austria
  • Feldbach, Austria, 8330
    • Novartis Investigative Site
  • Feldkirch, Austria, 6800
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  • Graz, Austria, A-8036
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  • Grieskirchen, Austria, 4710
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  • Linz, Austria, 4020
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  • Salzburg, Austria, 5020
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  • Thalheim bei Wels, Austria, 4600
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  • Vienna, Austria, A-1230
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  • Wels, Austria, 4600
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  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
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• Belgium
  • Aalst, Belgium, 9300
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  • Brussel, Belgium, 1090
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  • Bruxelles, Belgium, 1200
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  • Bruxelles, Belgium, 1070
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  • Bruxelles, Belgium, 1000
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  • Erpent, Belgium, 5101
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  • Gent, Belgium, 9000
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  • Gilly, Belgium, 6060
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  • Hasselt, Belgium, 3500
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  • Leuven, Belgium, 3000
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  • Liège, Belgium, 4000
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  • Luxembourg, Belgium, 1210
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  • Oostende, Belgium, 8400
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  • Roeselare, Belgium, 8800
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  • Turnhout, Belgium, 2300
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  • Wavre, Belgium, 1301
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  • BEL
    • Gosselies, BEL, Belgium, 6041
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  • Limburg
    • Genk, Limburg, Belgium, 3600
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• Bulgaria
  • Gabrovo, Bulgaria, 5300
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  • Pleven, Bulgaria, 5800
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  • Plovdiv, Bulgaria, 4002
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  • Ruse, Bulgaria, 7002
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  • Sofia, Bulgaria, 1431
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  • Stara Zagora, Bulgaria, 6000
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  • Troyan, Bulgaria, 5600
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  • Varna, Bulgaria, 9020
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• Canada
  • Quebec, Canada, G1N 4V3
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  • Alberta
    • Calgary, Alberta, Canada, T2N 4N1
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  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E1
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  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
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  • Ontario
    • Burlington, Ontario, Canada, L7N 3V2
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    • Downsview, Ontario, Canada, M3N 2Z9
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    • Toronto, Ontario, Canada, M5T 3A9
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  • Quebec
    • Mirabel, Quebec, Canada, J7J 2K8
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    • Montreal, Quebec, Canada, H3G 1L5
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    • Montreal, Quebec, Canada, H1M 1B1
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    • Sherbrooke, Quebec, Canada, J1H 5N4
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    • St-Charles-Borromée, Quebec, Canada, J6E 2B4
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• Chile
  • Quillota, Chile, 2260877
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  • Santiago, Chile, 8910131
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  • Santiago, Chile
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• China
  • Beijing, China, 100050
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  • Chongqing, China, 400037
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  • Chongqing, China, 400038
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  • Guang Zhou, China, 510010
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  • Shanghai, China, 200025
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  • Tianjin, China, 300052
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  • Beijing
    • Beijing, Beijing, China, 100730
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    • Beijing, Beijing, China, 100023
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  • Guangdong
    • Guang Zhou, Guangdong, China, 510120
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  • Hainan
    • Haikou, Hainan, China, 570311
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  • Hebei
    • Shijiazhuang, Hebei, China, 050000
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  • Hunan
    • Changsha, Hunan, China, 410003
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  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
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    • Suzhou, Jiangsu, China, 215006
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  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
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  • Liaoning
    • Shengyang, Liaoning, China, 110016
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  • Shanghai
    • Shanghai, Shanghai, China, 200433
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  • Shanxi
    • Xi'an, Shanxi, China, 710032
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  • Sichuan
    • Chengdu, Sichuan, China, 610041
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  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
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• Colombia
  • Armenia, Colombia
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  • Medellín, Colombia
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  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
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  • Santander
    • Floridablanca, Santander, Colombia, 57-7
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• Croatia
  • Karlovac, Croatia, 47000
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  • Zagreb, Croatia, 10000
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  • Zagreb, Croatia, 10 000
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• Czech Republic
  • Benesov, Czech Republic, 256 30
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  • Cesky Krumlov, Czech Republic, 381 01
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  • Cvikov, Czech Republic, 471 54
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  • Jindrichuv Hradec III, Czech Republic, 377 01
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  • Liberec, Czech Republic, 460 01
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  • Melnik, Czech Republic, 267 01
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  • Olomouc, Czech Republic, 775 20
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  • Ostrava, Czech Republic, 708 68
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  • Ostrava - Hrabuvka, Czech Republic, 70030
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  • Pardubice, Czech Republic, 530 09
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  • Prague 4, Czech Republic, 142 00
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  • Praha 10, Czech Republic, 108 00
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  • Praha 5, Czech Republic, 158 00
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  • Praha 6, Czech Republic, 169 00
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  • Praha 6 - Repy, Czech Republic, 163 00
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  • Strakonice, Czech Republic, 38601
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  • Teplice, Czech Republic, 415 01
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  • Zatec, Czech Republic, 438 01
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• Denmark
  • Aalborg, Denmark, DK-9000
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  • Copenhagen NV, Denmark, DK-2400
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  • Hellerup, Denmark, DK-2900
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  • Hvidovre, Denmark, DK-2650
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  • Næstved, Denmark, 4700
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  • Roskilde, Denmark, DK-4000
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  • Silkeborg, Denmark, 8600
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  • Sønderborg, Denmark, DK-6400
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  • Århus, Denmark, DK-8000
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• Estonia
  • Tallinn, Estonia, 13419
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  • Tallinn, Estonia, 13619
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  • Tartu, Estonia, 51014
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• Finland
  • HUS, Finland, 00029
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  • Helsinki, Finland, 00290
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  • Jyvaskyla, Finland, 40100
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  • Kuopio, Finland, FIN-70211
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  • Pori, Finland, FIN-28500
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  • Turku, Finland, FIN-20100
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• France
  • Angers, France, 49000
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  • Beuvry, France, 62660
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  • Briis Sous Forges, France, 91640
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  • Cournonterral, France, 34660
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  • Lyon cedex 04, France, 69317
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  • Montpellier, France, 34059
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  • Nantes, France, 44300
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  • Nantes, France, 44000
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  • Nimes Cedex, France, 30029
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  • Pessac, France, 33604
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  • Reims, France, 51092
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  • St Genis des Fontaines, France, 66740
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• Germany
  • Aschaffenburg, Germany, 63739
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  • Bad Woerishofen, Germany, 86825
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  • Bamberg, Germany, 96049
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  • Berlin, Germany, 12043
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  • Berlin, Germany, 12203
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  • Berlin, Germany, 13086
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  • Berlin, Germany, 10117
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  • Berlin, Germany, 10367
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  • Berlin, Germany, 13156
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  • Berlin, Germany, 10969
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  • Berlin, Germany, 10789
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  • Berlin, Germany, 10119
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  • Berlin, Germany, 12099
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  • Berlin, Germany, 13581
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  • Bielefeld, Germany, 33617
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  • Bochum, Germany, 44787
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  • Bonn, Germany, 53119
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  • Bonn, Germany, 53123
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  • Delitzsch, Germany, 04509
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  • Dresden, Germany, 01307
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  • Duisburg, Germany, 47057
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  • Erlangen, Germany, 91052
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  • Frankfurt, Germany, 60596
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  • Frankfurt, Germany, 60389
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  • Freudenberg, Germany, 57258
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  • Gauting, Germany, 82131
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  • Hagen, Germany, 59065
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  • Halle, Germany, 06108
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  • Hamburg, Germany, 20354
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  • Hamburg, Germany, 20253
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  • Hamburg, Germany, 22299
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  • Hannover Münden, Germany, 34346
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  • Kassel, Germany, 34121
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  • Koeln, Germany, 51069
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  • Landsberg, Germany, 86899
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  • Leipzig, Germany, 04207
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  • Leipzig, Germany, 04357
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  • Leipzig, Germany, 04103
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  • Leipzig, Germany, 04275
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  • Lübeck, Germany, 23552
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  • Lübeck, Germany, 23558
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  • Marburg, Germany, 35037
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  • Minden, Germany, 32423
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  • München, Germany, 80335
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  • Neu Isenburg, Germany, 63263
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  • Neumünster, Germany, 24534
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  • Oranienburg, Germany, 16515
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  • Potsdam, Germany, 14467
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  • Potsdam, Germany, 14469
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  • Prien a. Chiemsee, Germany, 83209
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  • Ratingen, Germany, 40878
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  • Reinfeld, Germany, 23858
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  • Rüdersdorf, Germany, 15562
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  • Schleswig, Germany, 24837
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  • Schwabach, Germany, 91126
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  • Solingen, Germany, 42651
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  • Stade, Germany, 21680
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  • Teuchern, Germany, 06682
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  • Ulm, Germany, 89073
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  • Warendorf, Germany, 48231
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  • Weinheim, Germany, 69469
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  • Wissen, Germany, 57537
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  • Witten, Germany, 58452
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  • Baden-Württemberg
    • Heidelberg, Baden-Württemberg, Germany, 69126
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  • NRW
    • Koblenz, NRW, Germany, 56068
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  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
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    • Peine, Niedersachsen, Germany, 31224
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  • Sachsen
    • Cottbus, Sachsen, Germany, 03050
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  • Schleswig Holstein
    • Geesthacht, Schleswig Holstein, Germany, 12502
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• Greece
  • Athens, Greece, 12462
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  • Athens, Greece, GR 115 27
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  • Heraklion Crete, Greece, GR 711 10
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  • Serres, Greece, GR 62 100
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  • Thessaloniki, Greece, GR 570 10
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  • GR
    • Athens, GR, Greece, 115 27
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    • Athens, GR, Greece, 106 76
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    • Larissa, GR, Greece, 411 10
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    • Rethymno, GR, Greece, 741 00
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    • Thessaloniki, GR, Greece, 564 03
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• Guatemala
  • Guatemala City, Guatemala, 01010
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  • Guatemala City, Guatemala, 01011
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  • Gautemala
    • Ciudad, Gautemala, Guatemala, 01010
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• Hong Kong
  • Kowloon, Hong Kong
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  • New Territories, Hong Kong
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• Hungary
  • Budapest, Hungary, 1125
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  • Budapest, Hungary, 1145
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  • Budapest, Hungary, 1121
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  • Deszk, Hungary, 6772
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  • Komarom, Hungary, 2900
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  • Torokbalint, Hungary, 2045
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• Iceland
  • Reykjavik, Iceland, IS-109
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• India
  • Bangalore, India, 560 034
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  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500004
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    • Vijayawada, Andhra Pradesh, India, 520 002
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    • Vishakhapatnam, Andhra Pradesh, India, 530002
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  • Gujarat
    • Ahmedabad, Gujarat, India, 380 060
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    • Ahmedabad, Gujarat, India, 380 008
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  • Haryana
    • Gurgaon, Haryana, India, 122 002
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  • Karnataka
    • Manipal, Karnataka, India, 576 104
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  • Maharashtra
    • Nagpur, Maharashtra, India, 400 012
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    • Nagpur, Maharashtra, India, 440010
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  • Punjab
    • Ludhiana, Punjab, India, 141001
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  • Tamil Nadu
    • Chennai, Tamil Nadu, India, 641037
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    • Coimbatore, Tamil Nadu, India, 641 045.
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    • Coimbatore, Tamil Nadu, India, 641037
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  • Tamilnadu
    • Coimbatore, Tamilnadu, India, 641 018
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  • West Bengal
    • Kolkata, West Bengal, India, 700 107
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• Italy
  • Napoli, Italy, 80131
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  • AN
    • Ancona, AN, Italy, 60020
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  • BA
    • Cassano delle Murge, BA, Italy, 70020
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    • Crema, CR, Italy, 26013
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    • Foggia, FG, Italy, 71100
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    • Firenze, FI, Italy, 50100
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    • Genova, GE, Italy, 16132
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    • Milano, MI, Italy, 20126
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  • MO
    • Pavullo nel Frignano, MO, Italy, 41026
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  • PA
    • Palermo, PA, Italy, 90146
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  • PD
    • Cittadella, PD, Italy, 35013
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    • Pordenone, PN, Italy, 33170
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    • Pavia, PV, Italy, 27100
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  • RE
    • Reggio Emilia, RE, Italy, 42123
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    • Cuasso al Monte, VA, Italy, 21050
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    • Tradate, VA, Italy, 21049
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  • VR
    • Negrar, VR, Italy, 37024
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• Japan
  • Fukuoka, Japan, 812-0033
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  • Kochi, Japan, 780-8077
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  • Aichi
    • Komaki-city, Aichi, Japan, 485-0041
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    • Nagoya, Aichi, Japan, 457-8511
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    • Seto-city, Aichi, Japan, 489-8642
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    • Toyoake-city, Aichi, Japan, 470-1192
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  • Fukuoka
    • Fukuoka-city, Fukuoka, Japan, 811-1394
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    • Yanagawa-city, Fukuoka, Japan, 832-0059
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  • Hokkaido
    • Asahikawa-city, Hokkaido, Japan, 070-8644
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    • Sapporo, Hokkaido, Japan, 062-8618
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    • Sapporo-city, Hokkaido, Japan, 060-8648
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  • Hyogo
    • Himeji-city, Hyogo, Japan, 672-8064
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  • Kagawa
    • Sakaide-city, Kagawa, Japan, 762-8550
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    • Takamatsu, Kagawa, Japan, 760-8538
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  • Kanagawa
    • Kawasaki-city, Kanagawa, Japan, 210-0852
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  • Kumamoto
    • Koshi-city, Kumamoto, Japan, 861-1196
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  • Kyoto
    • Kyoto-city, Kyoto, Japan, 606-8507
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  • Mie
    • Matsusaka-city, Mie, Japan, 515-8544
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  • Miyagi
    • Sendai-city, Miyagi, Japan, 980-8574
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  • Osaka
    • Kishiwada-city, Osaka, Japan, 596-8501
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  • Saitama
    • Koshigaya-city, Saitama, Japan, 343-0851
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  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8525
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    • Hamamatsu, Shizuoka, Japan, 434-8511
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    • Iwata, Shizuoka, Japan, 438-8550
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  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8431
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    • Chuo-ku, Tokyo, Japan, 103-0027
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    • Itabashi-ku, Tokyo, Japan, 173-8610
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    • Kiyose-city, Tokyo, Japan, 204-8585
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    • Meguro, Tokyo, Japan, 152-8902
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• Korea, Republic of
  • Incheon, Korea, Republic of, 403-720
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  • Seoul, Korea, Republic of, 156-755
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  • Seoul, Korea, Republic of, 130-872
    • Novartis Investigative Site
  • Seoul, Korea, Republic of, 136-705
    • Novartis Investigative Site
  • Gyeonggi-Do
    • Bucheon-Si, Gyeonggi-Do, Korea, Republic of, 14584
      • Novartis Investigative Site
  • Jeollabuk-do
    • Jeonju-si, Jeollabuk-do, Korea, Republic of, 561-712
      • Novartis Investigative Site
  • Korea
    • Seoul, Korea, Korea, Republic of, 03080
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 137-701
      • Novartis Investigative Site
    • Seoul, Korea, Korea, Republic of, 130-709
      • Novartis Investigative Site
• Latvia
  • Daugavpils, Latvia, LV-5401
    • Novartis Investigative Site
  • Riga, Latvia, 1002
    • Novartis Investigative Site
  • LV
    • Riga, LV, Latvia, LV-1038
      • Novartis Investigative Site
• Lithuania
  • Alytus, Lithuania, LT-62114
    • Novartis Investigative Site
  • Kaunas, Lithuania, LT-45130
    • Novartis Investigative Site
  • Klaipeda, Lithuania, 92288
    • Novartis Investigative Site
  • Klaipeda, Lithuania, LT-92231
    • Novartis Investigative Site
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • Vilnius, Lithuania, 06122
    • Novartis Investigative Site
  • LT
    • Kaunas, LT, Lithuania, 50128
      • Novartis Investigative Site
    • Vilnius, LT, Lithuania, 01117
      • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, 50009
      • Novartis Investigative Site
• Mexico
  • Aguascalientes, Mexico, 20230
    • Novartis Investigative Site
  • Mexico D.F., Mexico, 06726
    • Novartis Investigative Site
  • Puebla, Mexico, 72000
    • Novartis Investigative Site
  • Distrito Federal
    • Mexico, Distrito Federal, Mexico, 14050
      • Novartis Investigative Site
    • México, Distrito Federal, Mexico, 14080
      • Novartis Investigative Site
  • Jalisco
    • Guadalajara Jalisco, Jalisco, Mexico, 44220
      • Novartis Investigative Site
    • Zapopan, Jalisco, Mexico, 45200
      • Novartis Investigative Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • Novartis Investigative Site
  • Assen, Netherlands, 9401 RK
    • Novartis Investigative Site
  • Breda, Netherlands, 4818 CK
    • Novartis Investigative Site
  • Eindhoven, Netherlands, 5623 EJ
    • Novartis Investigative Site
  • Enschede, Netherlands, 7513 ER
    • Novartis Investigative Site
  • Geldrop, Netherlands, 5664 EH
    • Novartis Investigative Site
  • Groningen, Netherlands, 9728 NT
    • Novartis Investigative Site
  • Harderwijk, Netherlands, 3840 AC
    • Novartis Investigative Site
  • Zutphen, Netherlands, 7207 AE
    • Novartis Investigative Site
• Norway
  • Follebu, Norway, 2656
    • Novartis Investigative Site
  • Hønefoss, Norway, 3515
    • Novartis Investigative Site
  • Kløfta, Norway, 2040
    • Novartis Investigative Site
  • Kongsvinger, Norway, 2212
    • Novartis Investigative Site
  • Skedsmokorset, Norway, 2020
    • Novartis Investigative Site
  • Stavanger, Norway, 4005
    • Novartis Investigative Site
  • Svelvik, Norway, 3060
    • Novartis Investigative Site
  • Trondheim, Norway, 7006
    • Novartis Investigative Site
• Philippines
  • Bulacan, Philippines, 3020
    • Novartis Investigative Site
  • Quezon City, Philippines, 1100
    • Novartis Investigative Site
  • Batangas
    • Lipa City, Batangas, Philippines, 4217
      • Novartis Investigative Site
• Poland
  • Bialystok, Poland, 15-010
    • Novartis Investigative Site
  • Bialystok, Poland, 15-044
    • Novartis Investigative Site
  • Lodz, Poland, 90-153
    • Novartis Investigative Site
  • Pila, Poland, 64-920
    • Novartis Investigative Site
  • Poznan, Poland, 60-569
    • Novartis Investigative Site
  • Sopot, Poland, 81-741
    • Novartis Investigative Site
  • Wroclaw, Poland, 51-162
    • Novartis Investigative Site
• Portugal
  • Almada, Portugal, 2801-951
    • Novartis Investigative Site
  • Barcelos, Portugal, 4754-909
    • Novartis Investigative Site
  • Braga, Portugal, 4710-243
    • Novartis Investigative Site
  • Coimbra, Portugal, 3041-853
    • Novartis Investigative Site
  • Lisboa, Portugal, 1169-024
    • Novartis Investigative Site
  • Lisboa, Portugal, 1769-001
    • Novartis Investigative Site
  • Porto, Portugal, 4200-319
    • Novartis Investigative Site
  • Torres Vedras, Portugal, 2560-324
    • Novartis Investigative Site
  • Vila Franca de Xira, Portugal, 2600-009
    • Novartis Investigative Site
  • Vila Nova de Gaia, Portugal, 4434-502
    • Novartis Investigative Site
  • Viseu, Portugal, 3504-509
    • Novartis Investigative Site
• Romania
  • Arad, Romania, 310013
    • Novartis Investigative Site
  • Arad, Romania, 310086
    • Novartis Investigative Site
  • Brasov, Romania, 500086
    • Novartis Investigative Site
  • Bucharest, Romania, 060011
    • Novartis Investigative Site
  • Bucharest, Romania
    • Novartis Investigative Site
  • Bucharest, Romania, 050159
    • Novartis Investigative Site
  • Bucuresti, Romania, 50159
    • Novartis Investigative Site
  • Cluj-Napoca, Romania, 400371
    • Novartis Investigative Site
  • Deva, Romania, 330162
    • Novartis Investigative Site
  • Deva, Romania, 330084
    • Novartis Investigative Site
  • Iasi, Romania, 700305
    • Novartis Investigative Site
  • Oradea, Romania, 410051
    • Novartis Investigative Site
  • Targu Mures, Romania, 540072
    • Novartis Investigative Site
  • District 1
    • Bucuresti, District 1, Romania, 10457
      • Novartis Investigative Site
  • District 3
    • Bucharest, District 3, Romania, 030317
      • Novartis Investigative Site
  • Dolj
    • Craiova, Dolj, Romania, 200515
      • Novartis Investigative Site
  • Jud. Iasi
    • Iasi, Jud. Iasi, Romania, 700115
      • Novartis Investigative Site
  • Timis
    • Timisoara, Timis, Romania, 300310
      • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656045
    • Novartis Investigative Site
  • Chelyabinsk, Russian Federation, 454021
    • Novartis Investigative Site
  • Kazan, Russian Federation, 420012
    • Novartis Investigative Site
  • N.Novgorod, Russian Federation, 603126
    • Novartis Investigative Site
  • Rostov-on-Don, Russian Federation, 344090
    • Novartis Investigative Site
  • Ryazan, Russian Federation, 390026
    • Novartis Investigative Site
  • Saratov, Russian Federation, 410012
    • Novartis Investigative Site
  • Tver, Russian Federation, 170100
    • Novartis Investigative Site
  • Ufa, Russian Federation, 450000
    • Novartis Investigative Site
  • Yaroslavl, Russian Federation, 150030
    • Novartis Investigative Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novartis Investigative Site
  • Belgrade, Serbia, 11080
    • Novartis Investigative Site
  • Knez Selo, Serbia, 18204
    • Novartis Investigative Site
  • Kragujevac, Serbia, 34000
    • Novartis Investigative Site
• Slovakia
  • Bratislava, Slovakia, 84104
    • Novartis Investigative Site
  • Kosice, Slovakia, 040 01
    • Novartis Investigative Site
  • Lucenec, Slovakia, 98439
    • Novartis Investigative Site
  • Martin, Slovakia, 036 59
    • Novartis Investigative Site
  • Nove Zamky, Slovakia, 940 01
    • Novartis Investigative Site
  • Poprad, Slovakia, 058 01
    • Novartis Investigative Site
  • Povazska Bystrica, Slovakia, 017 01
    • Novartis Investigative Site
  • Spisská Nová Ves, Slovakia, 052 01
    • Novartis Investigative Site
  • Slovak Republic
    • Bardejov, Slovak Republic, Slovakia, 085 01
      • Novartis Investigative Site
    • Bojnice, Slovak Republic, Slovakia, 972 01
      • Novartis Investigative Site
    • Liptovsky Hradok, Slovak Republic, Slovakia, 033 01
      • Novartis Investigative Site
    • Partizanske, Slovak Republic, Slovakia, 958 01
      • Novartis Investigative Site
  • Slovak republic
    • Humenné, Slovak republic, Slovakia, 066 01
      • Novartis Investigative Site
    • Kosice, Slovak republic, Slovakia, 04001
      • Novartis Investigative Site
  • Slovensko
    • Námestovo, Slovensko, Slovakia, 02901
      • Novartis Investigative Site
• South Africa
  • Cape Town, South Africa, 7500
    • Novartis Investigative Site
  • Cape Town, South Africa, 7531
    • Novartis Investigative Site
  • Cape Town, South Africa, 7925
    • Novartis Investigative Site
  • Cape Town, South Africa, 7505
    • Novartis Investigative Site
  • Gatesville, South Africa, 7764
    • Novartis Investigative Site
  • Port Elizabeth, South Africa, 6014
    • Novartis Investigative Site
  • Pretoria, South Africa, 0181
    • Novartis Investigative Site
  • Pretoria, South Africa, 0132
    • Novartis Investigative Site
  • Durban
    • Berea, Durban, South Africa, 4001
      • Novartis Investigative Site
  • Gauteng
    • Sandton, Gauteng, South Africa, 2057
      • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08022
    • Novartis Investigative Site
  • Madrid, Spain, 28046
    • Novartis Investigative Site
  • Madrid, Spain, 28029
    • Novartis Investigative Site
  • Andalucia
    • Cordoba, Andalucia, Spain, 14004
      • Novartis Investigative Site
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sanlucar de Barrameda, Andalucia, Spain, 11540
      • Novartis Investigative Site
  • Asturias
    • Oviedo, Asturias, Spain, 33006
      • Novartis Investigative Site
  • Cantabria
    • Torrelavega, Cantabria, Spain, 39300
      • Novartis Investigative Site
  • Castilla y Leon
    • Burgos, Castilla y Leon, Spain, 09006
      • Novartis Investigative Site
    • Ponferrada, Castilla y Leon, Spain, 24400
      • Novartis Investigative Site
    • Valladolid, Castilla y Leon, Spain, 47011
      • Novartis Investigative Site
  • Cataluna
    • Barcelona, Cataluna, Spain, 08026
      • Novartis Investigative Site
  • Catalunya
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Cataluña
    • Barcelona, Cataluña, Spain, 08024
      • Novartis Investigative Site
    • Salt, Cataluña, Spain, 17190
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Alicante, Comunidad Valenciana, Spain, 03550
      • Novartis Investigative Site
    • Alzira, Comunidad Valenciana, Spain, 46600
      • Novartis Investigative Site
    • Valencia, Comunidad Valenciana, Spain, 46014
      • Novartis Investigative Site
  • Extremadura
    • Merida, Extremadura, Spain, 06800
      • Novartis Investigative Site
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Novartis Investigative Site
  • Murcia
    • Cartagena, Murcia, Spain, 30202
      • Novartis Investigative Site
  • Vizcaya
    • Baracaldo, Vizcaya, Spain, 48903
      • Novartis Investigative Site
• Sweden
  • Boras, Sweden, 506 30
    • Novartis Investigative Site
  • Luleå, Sweden, SE-971 80
    • Novartis Investigative Site
  • Lund, Sweden, SE-221 85
    • Novartis Investigative Site
  • Stockholm, Sweden, 111 57
    • Novartis Investigative Site
  • Trollhattan, Sweden, 461 85
    • Novartis Investigative Site
  • Uddevalla, Sweden, 451 50
    • Novartis Investigative Site
• Taiwan
  • Chiayi County, Taiwan, 613
    • Novartis Investigative Site
  • Niaosong Township, Taiwan, 83301
    • Novartis Investigative Site
  • Taichung, Taiwan, 40447
    • Novartis Investigative Site
  • Taichung, Taiwan, 40705
    • Novartis Investigative Site
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
  • Taipei, Taiwan, 112
    • Novartis Investigative Site
  • Taipei County, Taiwan, 22060
    • Novartis Investigative Site
  • Taiwan ROC
    • Tainan 704, Taiwan ROC, Taiwan
      • Novartis Investigative Site
• Thailand
  • Bangkok, Thailand, 10700
    • Novartis Investigative Site
  • Chiang Mai, Thailand, 50200
    • Novartis Investigative Site
  • Khon Kaen, Thailand, 40002
    • Novartis Investigative Site
  • Songkla, Thailand, 90110
    • Novartis Investigative Site
• Turkey
  • Ankara, Turkey, 06100
    • Novartis Investigative Site
  • Ankara, Turkey, 06490
    • Novartis Investigative Site
  • Istanbul, Turkey, 34854
    • Novartis Investigative Site
  • Istanbul, Turkey
    • Novartis Investigative Site
  • Izmir, Turkey, 35040
    • Novartis Investigative Site
  • Kinikli / Denizli, Turkey, 20070
    • Novartis Investigative Site
  • Manisa, Turkey, 45040
    • Novartis Investigative Site
  • Mersin, Turkey, 33079
    • Novartis Investigative Site
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Novartis Investigative Site
  • Cambridge, United Kingdom, CB7 5JD
    • Novartis Investigative Site
  • Chester, United Kingdom, CH2 1UL
    • Novartis Investigative Site
  • Darlington, United Kingdom, DL3 6HX
    • Novartis Investigative Site
  • Lancashire, United Kingdom, FY3 7EN
    • Novartis Investigative Site
  • Leeds, United Kingdom, LS9 7TF
    • Novartis Investigative Site
  • London, United Kingdom, EC14 7BE
    • Novartis Investigative Site
  • Newcastle-upon-Tyne, United Kingdom, NE7 7DN
    • Novartis Investigative Site
  • Southampton, United Kingdom, SO16 6YD
    • Novartis Investigative Site
  • Tyne & Wear, United Kingdom, NE29 8NH
    • Novartis Investigative Site
  • Wiltshire, United Kingdom, SN15 2SB
    • Novartis Investigative Site
  • Cambridgeshire
    • Huntingdon, Cambridgeshire, United Kingdom, PE29 6NT
      • Novartis Investigative Site
  • Cleveland
    • Stockton, Cleveland, United Kingdom, TS19 8PE
      • Novartis Investigative Site
  • Radstock
    • Midsomer Norton, Radstock, United Kingdom, BA3 2UH
      • Novartis Investigative Site
  • Somerset
    • Axbridge, Somerset, United Kingdom, BS26 2BJ
      • Novartis Investigative Site
    • Taunton, Somerset, United Kingdom, TA1 5DA
      • Novartis Investigative Site
  • Tyne and Wear
    • South Shields, Tyne and Wear, United Kingdom, NE34 0PL
      • Novartis Investigative Site
  • West Sussex
    • Crawley, West Sussex, United Kingdom, RH10 7DX
      • Novartis Investigative Site
  • West Yorkshire
    • Bradford, West Yorkshire, United Kingdom, BD9 6RJ
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent must be obtained before any assessment is performed
• Male or female adults aged ≥40 years
• Patients with stable Chronic Obstructive Pulmonary Disease ( COPD) according to the current GOLD strategy (GOLD 2011)
• Current or ex-smokers who have a smoking history of at least 10 pack years. (Ten pack-years are defined as 20 cigarettes a day for 10 years, or 10 cigarettes a day for 20 years)
• Patients with a post-bronchodilator Forced Expiratory Volume in one second (FEV1) ≥25 and < 60% of the predicted normal value, and post-bronchodilator FEV1/FVC (Forced Vital Capacity) < 0.70 at day -28. (Post refers to 1 hour after sequential inhalation of 84 µg (or equivalent dose) of ipratropium bromide and 400 µg of salbutamol)
• A documented history of at least 1 COPD exacerbation in the previous 12 months that required treatment with systemic glucocorticosteroids and/or antibiotics
• Patients taking stable COPD medication (at least 60 days) prior to day 28
• Patients with an mMRC grade of at least 2 at day 28

Exclusion Criteria:

• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG (human Chorionic Gonadotropin) laboratory test
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential
• Patients with Type I or uncontrolled Type II diabetes
• Patients with a history of long QT syndrome or whose QTc measured at day 28 (Fridericia method) is prolonged (>450 ms for males and females) and confirmed by a central assessor. These patients should not be re-screened
• Patients who have a clinically significant ECG abnormality prior to randomization. (These patients should not be re-screened)
• Patients who have a clinically significant laboratory abnormality at screening
• Patients who have clinically significant renal, cardiovascular (such as but not limited to unstable ischemic heart disease, NYHA Class III/IV left ventricular failure, myocardial infarction), arrhythmia (see below for patients with atrial fibrillation), neurological, endocrine, immunological, psychiatric, gastrointestinal, hepatic, or hematological abnormalities which could interfere with the assessment of the efficacy and safety of the study treatment
• Patients with paroxysmal (e.g. intermittent) atrial fibrillation are excluded
• Patients with persistent atrial fibrillation as defined by continuous atrial fibrillation for at least 6 months and controlled with a rate control strategy (i.e., selective beta blocker, calcium channel blocker, pacemaker placement, digoxin or ablation therapy) for at least 6 months may be considered for inclusion. In such patients, atrial fibrillation must be present at both pre-randomization visits, with a resting ventricular rate < 100/min. At screening the atrial fibrillation must be confirmed by central reading
• Patients contraindicated for treatment with, or having a history of reactions/ hypersensitivity to any of the following inhaled drugs, drugs of a similar class or any component thereof: anticholinergic agents, long and short acting beta-2 agonists, sympathomimetic amines, lactose or any of the other excipients of trial medication
• Patients with a history of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
• Patients with narrow-angle glaucoma, symptomatic benign prostatic hyperplasia or bladder-neck obstruction or moderate to severe renal impairment or urinary retention. Benign Prostatic Hyperplasia (BPH) patients who are stable on treatment can be considered
• Patients who have not achieved an acceptable spirometry results at screening in accordance with American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria for acceptability (one retest may be performed for patients that don't meet the acceptability criteria)
• Patients who have had a COPD exacerbation that required treatment with antibiotics and/or systemic corticosteroids and/or hospitalization in the 6 weeks prior to screening
• Patients who develop a COPD exacerbation of any severity (mild/moderate/severe) between screening and treatment will not be eligible but will be permitted to be re-screened after a minimum of 6 weeks after the resolution of the COPD exacerbation
• Patients who have had a respiratory tract infection within 4 weeks prior to screening
• Patients who develop a respiratory tract infection between screening and prior to treatment will not be eligible, but will be permitted to be re-screened 4 weeks after the resolution of the respiratory tract infection
• Patients requiring long term oxygen therapy prescribed for >12 hours per day
• Patients with any history of asthma
• Patients with an onset of respiratory symptoms, including a COPD diagnosis prior to age 40 years
• Patients with a blood eosinophil count > 600/mm3 at screening
• Patients with allergic rhinitis who use a H1 antagonist or intra-nasal corticosteroids intermittently (treatment with a stable dose or regimen is permitted)
• Patients with concomitant pulmonary disease (e.g. lung fibrosis, sarcoidosis, interstitial lung disease, pulmonary hypertension)
• Patients with clinically significant bronchiectasis
• Patients with a diagnosis of α-1 anti-trypsin deficiency
• Patients with active pulmonary tuberculosis, unless confirmed by imaging to be no longer active
• Patients with pulmonary lobectomy or lung volume reduction surgery or lung transplantation
• Patients participating in or planning to participate in the active phase of a supervised pulmonary rehabilitation program during the study. (Maintenance program is permitted.)
• Patients receiving any medications in the classes listed in the protocol
• Patients receiving any COPD related medications in the classes specified in the protocol must undergo the required washout period prior to screening and follow the adjustment to treatment program
• Use of other investigational drugs/devices (approved or unapproved) at the time of enrollment, or within 30 days or 5 half-lives of screening, whichever is longer
• Patients unable to use an electronic patient diary and EXACT pro diary
• Patients unable to use a dry powder inhaler device, Metered Dose Inhaler (MDI) or a pressurized MDI (rescue medication) or comply with the study regimen.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: QVA149; QVA149 (110/50 μg) once daily	Drug: QVA149; QVA149 will be supplied in a capsule form in blister packs for use in the Novartis Concept 1 SDDPI.
Active Comparator: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS); Salmeterol/fluticasone (50/500μg) b.i.d	Drug: Long acting B2 agonist (LABA) and inhaled corticosteroid (ICS); Salmeterol/fluticasone dry inhalation powder delivered via the Accuhaler device.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of COPD Exacerbations	COPD exacerbations starting between first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event. Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. As the offset variable log(exposure time in years) was used.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First COPD Exacerbation.	First COPD exacerbations starting between first dose and one day after last treatment are included. Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region.	52 weeks
Rate of Moderate to Severe COPD Exacerbations.	COPD exacerbations starting between date of first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event with the worst severity. A COPD exacerbation of moderate severity meets the symptoms definition in the protocol and requires treatment with systemic corticosteroids and/or antibiotics. A severe COPD exacerbation requires hospitalization. Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used.	52 weeks
Time to First Moderate to Severe COPD Exacerbation.	First COPD exacerbations starting between first dose and one day after last treatment are included. Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region.	52 weeks.
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids	COPD exacerbations starting between date of first dose and one day after last treatment are included. COPD exacerbations that occurred within 7 days of each other are collapsed as one event with the worst severity. Estimates are from a generalized linear model assuming a negative binomial distribution with fixed effects of treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used.	52 weeks
Rate of Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics	Estimates are from a generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used. COPD exacerbations starting between first dose and one day after last treatment are included .	52 weeks
Rate of Moderate to Severe COPD Exacerbations Requiring Hospitalization. COPD Exacerbations Starting Between First Dose and One Day After Last Treatment Are Included.	All exacerbations requiring hospitalization are considered severe according to protocol definitions so this is the rate of severe COPD exacerbations only. Note - an ER visit of longer than 24 hours was considered a hospitalization.	52 weeks
Rate of Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days	Re-hospitalizations are defined as hospitalizations starting within the first 30 days after a severe COPD exacerbation and between first dose and one day after date of last treatment. Generalized linear model assuming a negative binomial distribution with terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. The offset variable log(exposure time in years) was used. COPD exacerbations starting between first dose and one day after last treatment are included.	52 weeks
Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Systemic Corticosteroids	Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.	52 weeks
Time to First Moderate to Severe COPD Exacerbations Requiring Treatment With Antibiotics	Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.	52 weeks
Time to First Moderate to Severe COPD Exacerbations Requiring Hospitalization	Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.	52 weeks
Time to First Moderate to Severe COPD Exacerbations Requiring Re-hospitalization Within 30 Days	Cox regression model includes terms for treatment, baseline total symptom score, baseline COPD exacerbation history (i.e. number of COPD exacerbations during the past 12 months prior to study), smoking status at screening, ICS use at screening, airflow limitation severity, and region. COPD exacerbations starting between first dose and one day after date of last treatment are included.	52 weeks
Forced Expiratory Volume in 1 Second	Change from baseline. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, region, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, day 1 (30 min and one hour post dose)
Forced Expiratory Volume in 1 Second	Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, 4 weeks
Forced Expiratory Volume in 1 Second	Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, 12 weeks
Forced Expiratory Volume in 1 Second	Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, 26 weeks
Forced Expiratory Volume in 1 Second	Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, 38 weeks
Forced Expiratory Volume in 1 Second	Change from baseline in trough value. Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, airflow limitation severity, visit, treatment-by-visit interaction, and baseline FEV1-by-visit interaction.	Baseline, 52 weeks
Change From Baseline in Forced Expiratory Volume in 1 Second AUC (0-12h)	Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FEV1 was defined as the average of the pre-dose FEV1 measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FEV1 measurements, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, region, baseline FEV1 * visit interaction, and visit, treatment * visit interaction. The trapezoidal rule was used to calculate FEV1 AUC and then normalized to the length of time"	Baseline, 52 weeks
Change From Baseline in Total St. George's Respiratory Questionnaire Score	The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.	Baseline, 4 weeks
Change From Baseline in Total St. George's Respiratory Questionnaire Score	The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.	Baseline, 12 weeks
Change From Baseline in Total St. George's Respiratory Questionnaire Score	The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.	Baseline, 26 weeks
Change From Baseline in Total St. George's Respiratory Questionnaire Score	The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.	Baseline, 38 weeks
Change From Baseline in Total St. George's Respiratory Questionnaire Score	The St. George Respiratory Questionnaire C (SGRQ-C) is a disease-specific measure of health status for use in COPD that was used to provide the health status measurements in this study. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline SGRQ-C total score, smoking status at baseline, baseline inhaled corticosteroid (ICS) use, airflow limitation severity, visit, treatment*visit Interaction, baseline SGRQ-C total score*visit + region. lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of health status. A negative change from baseline indicates improvement.	Baseline, 52 weeks
Change From Baseline in the Number of Puffs of Rescue Medication	A linear mixed model (LMM) was used for this analysis Change from baseline in mean number of puffs. LMM including: treatment, baseline value, smoking status at screening, ICS use at screening, airflow limitation severity, region and random effect of center nested within region.	Baseline, 52 weeks
Change From Baseline in the Safety of QVA149 ((110/50 μg o.d.) vs Fluticasone/Salmeterol (500/50μg Bid) in Terms of HPA Axis Function, as Determined by Collection of 24-hour Urine Cortisol.	Urine cortisol/creatinine ratio	Baseline, 52 Weeks
Change From Baseline in Forced Vital Capacity	Change from baseline in trough value (average of values measured 45 and 15 minutes prior to the morning dose). Pulmonary function assessments were performed using centralized spirometry according to international standards. Baseline FVC was defined as the average of the pre-dose FVC measured at -45 minutes (min) and -15 min at day 1. A mixed model for repeated measures (MMRM), used for this analysis, included terms of treatment, baseline FVC measurements, smoking status at screening, screening inhaled corticosteroid (ICS) use, region, baseline FVC * visit interaction, and visit, treatment * visit interaction	4 Weeks, 12 Weeks, 26 Weeks, 38 Weeks, 52 Weeks
Number of Patients With Adverse Events, Serious Adverse Events, and Death	The overall rate of adverse events reported from initiation through 30 days post last dose.	52 weeks of treatment + 30 days

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Mackay AJ, Kostikas K, Roche N, Frent SM, Olsson P, Pfister P, Gupta P, Patalano F, Banerji D, Wedzicha JA. Impact of baseline symptoms and health status on COPD exacerbations in the FLAME study. Respir Res. 2020 Apr 22;21(1):93. doi: 10.1186/s12931-020-01354-8.
• Wedzicha JA, Singh D, Tsiligianni I, Jenkins C, Fucile S, Fogel R, Shen S, Goyal P, Mezzi K, Kostikas K. Treatment response to indacaterol/glycopyrronium versus salmeterol/fluticasone in exacerbating COPD patients by gender: a post-hoc analysis in the FLAME study. Respir Res. 2019 Jan 8;20(1):4. doi: 10.1186/s12931-019-0972-7.
• Frent SM, Chapman KR, Larbig M, Mackay A, Fogel R, Gutzwiller FS, Shen S, Patalano F, Banerji D, Kostikas K, Wedzicha JA. Capturing Exacerbations of Chronic Obstructive Pulmonary Disease with EXACT. A Subanalysis of FLAME. Am J Respir Crit Care Med. 2019 Jan 1;199(1):43-51. doi: 10.1164/rccm.201801-0038OC.
• Anzueto AR, Kostikas K, Mezzi K, Shen S, Larbig M, Patalano F, Fogel R, Banerji D, Wedzicha JA. Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study. Respir Res. 2018 Jun 20;19(1):121. doi: 10.1186/s12931-018-0830-z.
• Roche N, Chapman KR, Vogelmeier CF, Herth FJF, Thach C, Fogel R, Olsson P, Patalano F, Banerji D, Wedzicha JA. Blood Eosinophils and Response to Maintenance Chronic Obstructive Pulmonary Disease Treatment. Data from the FLAME Trial. Am J Respir Crit Care Med. 2017 May 1;195(9):1189-1197. doi: 10.1164/rccm.201701-0193OC.
• Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, Thach C, Fogel R, Patalano F, Vogelmeier CF; FLAME Investigators. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. N Engl J Med. 2016 Jun 9;374(23):2222-34. doi: 10.1056/NEJMoa1516385. Epub 2016 May 15.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: January 30, 2013
• First Submitted That Met QC Criteria: January 30, 2013
• First Posted (Estimate): February 1, 2013

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: May 5, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Keywords: COPD, QVA149, FLAME( EFfect of Indacaterol Glycopyronium Vs Fluticasone salmeterol on COPD Exacerbations)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: CQVA149A2318