Tiotropium +Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)

A Randomised, Double-blind, Parallel Group Study to Assess the Efficacy and Safety of 52 Weeks of Once Daily Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (2.5 µg / 5 µg; 5 µg / 5 µg) (Delivered by the Respimat® Inhaler) Compared With the Individual Components (2.5 µg and 5 µg Tiotropium, 5 µg Olodaterol) (Delivered by the Respimat® Inhaler) in Patients With Chronic Obstructive Pulmonary Disease (COPD) [TOnado TM 2]

The overall objective of this study is to assess the efficacy and safety of 52 weeks once daily treatment with orally inhaled tiotropium + olodaterol FDC (delivered by the RESPIMAT Inhaler) compared with the individual components (tiotropium, olodaterol) (delivered by the RESPIMAT Inhaler) in patients with COPD.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Device: Respimat; Drug: tiotropium + olodaterol; Drug: olodaterol; Drug: tiotropium

• Study Type: Interventional
• Enrollment (Actual): 2539
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Feldbach, Austria
    • 1237.6.43006 Boehringer Ingelheim Investigational Site
  • Gänserndorf, Austria
    • 1237.6.43005 Boehringer Ingelheim Investigational Site
  • Innsbruck, Austria
    • 1237.6.43002 Boehringer Ingelheim Investigational Site
  • Leoben, Austria
    • 1237.6.43004 Boehringer Ingelheim Investigational Site
  • Linz, Austria
    • 1237.6.43001 Boehringer Ingelheim Investigational Site
  • Salzburg, Austria
    • 1237.6.43003 Boehringer Ingelheim Investigational Site
• Belgium
  • Brussel, Belgium
    • 1237.6.32007 Boehringer Ingelheim Investigational Site
  • Bruxelles, Belgium
    • 1237.6.32005 Boehringer Ingelheim Investigational Site
  • Gent, Belgium
    • 1237.6.32004 Boehringer Ingelheim Investigational Site
  • Jambes, Belgium
    • 1237.6.32002 Boehringer Ingelheim Investigational Site
  • Lebbeke, Belgium
    • 1237.6.32009 Boehringer Ingelheim Investigational Site
  • Leuven, Belgium
    • 1237.6.32001 Boehringer Ingelheim Investigational Site
  • Liège, Belgium
    • 1237.6.32006 Boehringer Ingelheim Investigational Site
  • Oostende, Belgium
    • 1237.6.32008 Boehringer Ingelheim Investigational Site
  • Turnhout, Belgium
    • 1237.6.32010 Boehringer Ingelheim Investigational Site
• Brazil
  • Botucatu, Brazil
    • 1237.6.55013 Boehringer Ingelheim Investigational Site
  • Florianopolis, Brazil
    • 1237.6.55010 Boehringer Ingelheim Investigational Site
  • Passo Fundo, Brazil
    • 1237.6.55012 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1237.6.55001 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1237.6.55002 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1237.6.55003 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1237.6.55005 Boehringer Ingelheim Investigational Site
  • Porto Alegre, Brazil
    • 1237.6.55009 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1237.6.55006 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1237.6.55007 Boehringer Ingelheim Investigational Site
  • Sao Paulo, Brazil
    • 1237.6.55011 Boehringer Ingelheim Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • 1237.6.02109 Boehringer Ingelheim Investigational Site
  • British Columbia
    • Vancouver, British Columbia, Canada
      • 1237.6.02111 Boehringer Ingelheim Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada
      • 1237.6.02106 Boehringer Ingelheim Investigational Site
  • Ontario
    • Courtice, Ontario, Canada
      • 1237.6.02110 Boehringer Ingelheim Investigational Site
    • Downsview, Ontario, Canada
      • 1237.6.02101 Boehringer Ingelheim Investigational Site
    • Sarnia, Ontario, Canada
      • 1237.6.02112 Boehringer Ingelheim Investigational Site
    • Toronto, Ontario, Canada
      • 1237.6.02103 Boehringer Ingelheim Investigational Site
    • Windsor, Ontario, Canada
      • 1237.6.02102 Boehringer Ingelheim Investigational Site
  • Quebec
    • Point Claire, Quebec, Canada
      • 1237.6.02104 Boehringer Ingelheim Investigational Site
    • Sherbrooke, Quebec, Canada
      • 1237.6.02105 Boehringer Ingelheim Investigational Site
    • Ste-Foy, Quebec, Canada
      • 1237.6.02108 Boehringer Ingelheim Investigational Site
• China
  • Baotou, China
    • 1237.6.86117 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1237.6.86102 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1237.6.86104 Boehringer Ingelheim Investigational Site
  • Beijing, China
    • 1237.6.86105 Boehringer Ingelheim Investigational Site
  • Changsha, China
    • 1237.6.86115 Boehringer Ingelheim Investigational Site
  • Chengdu, China
    • 1237.6.86110 Boehringer Ingelheim Investigational Site
  • Chongqing, China
    • 1237.6.86111 Boehringer Ingelheim Investigational Site
  • Haikou, China
    • 1237.6.86109 Boehringer Ingelheim Investigational Site
  • Hangzhou, China
    • 1237.6.86108 Boehringer Ingelheim Investigational Site
  • Hohhot, China
    • 1237.6.86116 Boehringer Ingelheim Investigational Site
  • Jinan, China
    • 1237.6.86114 Boehringer Ingelheim Investigational Site
  • Nanjing, China
    • 1237.6.86106 Boehringer Ingelheim Investigational Site
  • Shanghai, China
    • 1237.6.86101 Boehringer Ingelheim Investigational Site
  • Shenyang, China
    • 1237.6.86113 Boehringer Ingelheim Investigational Site
  • Suzhou, China
    • 1237.6.86107 Boehringer Ingelheim Investigational Site
  • Xi'An, China
    • 1237.6.86112 Boehringer Ingelheim Investigational Site
• Colombia
  • Bogota, Colombia
    • 1237.6.57008 Boehringer Ingelheim Investigational Site
  • Bogota DC, Colombia
    • 1237.6.57001 Boehringer Ingelheim Investigational Site
  • Bogota DC, Colombia
    • 1237.6.57003 Boehringer Ingelheim Investigational Site
  • Bogota DC, Colombia
    • 1237.6.57007 Boehringer Ingelheim Investigational Site
  • Cali, Colombia
    • 1237.6.57006 Boehringer Ingelheim Investigational Site
  • Floridablanca, Colombia
    • 1237.6.57004 Boehringer Ingelheim Investigational Site
• Croatia
  • Petrinja, Croatia
    • 1237.6.38503 Boehringer Ingelheim Investigational Site
  • Rijeka, Croatia
    • 1237.6.38504 Boehringer Ingelheim Investigational Site
  • Zadar, Croatia
    • 1237.6.38502 Boehringer Ingelheim Investigational Site
  • Zagreb, Croatia
    • 1237.6.38501 Boehringer Ingelheim Investigational Site
• Germany
  • Aschaffenburg, Germany
    • 1237.6.49022 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1237.6.49017 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1237.6.49026 Boehringer Ingelheim Investigational Site
  • Frankfurt, Germany
    • 1237.6.49027 Boehringer Ingelheim Investigational Site
  • Großhansdorf, Germany
    • 1237.6.49025 Boehringer Ingelheim Investigational Site
  • Halle, Germany
    • 1237.6.49016 Boehringer Ingelheim Investigational Site
  • Hamburg, Germany
    • 1237.6.49024 Boehringer Ingelheim Investigational Site
  • Hannover, Germany
    • 1237.6.49021 Boehringer Ingelheim Investigational Site
  • Leipzig, Germany
    • 1237.6.49019 Boehringer Ingelheim Investigational Site
  • Mainz, Germany
    • 1237.6.49028 Boehringer Ingelheim Investigational Site
  • Rodgau/Dudenhofen, Germany
    • 1237.6.49018 Boehringer Ingelheim Investigational Site
  • Schwerin, Germany
    • 1237.6.49020 Boehringer Ingelheim Investigational Site
  • Teuchern, Germany
    • 1237.6.49023 Boehringer Ingelheim Investigational Site
• Hungary
  • Debrecen, Hungary
    • 1237.6.36001 Boehringer Ingelheim Investigational Site
  • Gödöllö, Hungary
    • 1237.6.36004 Boehringer Ingelheim Investigational Site
  • Pecs, Hungary
    • 1237.6.36005 Boehringer Ingelheim Investigational Site
  • Sopron, Hungary
    • 1237.6.36003 Boehringer Ingelheim Investigational Site
  • Szeged, Hungary
    • 1237.6.36002 Boehringer Ingelheim Investigational Site
• India
  • Chennai, India
    • 1237.6.91003 Boehringer Ingelheim Investigational Site
  • Coimbatore, India
    • 1237.6.91011 Boehringer Ingelheim Investigational Site
  • Jaipur, India
    • 1237.6.91004 Boehringer Ingelheim Investigational Site
  • Kolkatta, India
    • 1237.6.91002 Boehringer Ingelheim Investigational Site
  • Maharastra, India
    • 1237.6.91007 Boehringer Ingelheim Investigational Site
  • Mumbai, India
    • 1237.6.91006 Boehringer Ingelheim Investigational Site
  • Nashik, Maharashtra, India
    • 1237.6.91009 Boehringer Ingelheim Investigational Site
  • Pune, India
    • 1237.6.91008 Boehringer Ingelheim Investigational Site
• Ireland
  • County Limerick, Ireland
    • 1237.6.35304 Boehringer Ingelheim Investigational Site
  • Dublin 24, Ireland
    • 1237.6.35303 Boehringer Ingelheim Investigational Site
  • Dublin 4, Ireland
    • 1237.6.35301 Boehringer Ingelheim Investigational Site
• Japan
  • Abeno-ku, Osaka, Osaka, Japan
    • 1237.6.81127 Boehringer Ingelheim Investigational Site
  • Aoi-ku, Shizuoka, Shizuoka, Japan
    • 1237.6.81123 Boehringer Ingelheim Investigational Site
  • Chuo-ku, Kobe, Hyogo, Japan
    • 1237.6.81132 Boehringer Ingelheim Investigational Site
  • Fukui, Fukui, Japan
    • 1237.6.81121 Boehringer Ingelheim Investigational Site
  • Fukuyama, Hiroshima, Japan
    • 1237.6.81137 Boehringer Ingelheim Investigational Site
  • Hachioji, Tokyo, Japan
    • 1237.6.81109 Boehringer Ingelheim Investigational Site
  • Himeji, Hyogo, Japan
    • 1237.6.81134 Boehringer Ingelheim Investigational Site
  • Hitachi, Ibaraki, Japan
    • 1237.6.81106 Boehringer Ingelheim Investigational Site
  • Iizuka, Fukuoka, Japan
    • 1237.6.81139 Boehringer Ingelheim Investigational Site
  • Iwamizawa, Hokkaido, Japan
    • 1237.6.81102 Boehringer Ingelheim Investigational Site
  • Kamakura, Kanagawa, Japan
    • 1237.6.81117 Boehringer Ingelheim Investigational Site
  • Kanazawa, Ishikawa, Japan
    • 1237.6.81120 Boehringer Ingelheim Investigational Site
  • Kanazawa, Yokohama, Kanagawa, Japan
    • 1237.6.81113 Boehringer Ingelheim Investigational Site
  • Kashiwa, Chiba, Japan
    • 1237.6.81108 Boehringer Ingelheim Investigational Site
  • Kawasaki-ku, Kawasaki, Kanagawa, Japan
    • 1237.6.81114 Boehringer Ingelheim Investigational Site
  • Kita-ku, Okayama, Okayama, Japan
    • 1237.6.81135 Boehringer Ingelheim Investigational Site
  • Kita-ku, Sakai, Osaka, Japan
    • 1237.6.81126 Boehringer Ingelheim Investigational Site
  • Kita-ku, Sapporo, Hokkaido, Japan
    • 1237.6.81101 Boehringer Ingelheim Investigational Site
  • Kurashiki, Okayama, Japan
    • 1237.6.81136 Boehringer Ingelheim Investigational Site
  • Minami-ku, Yokohama, Kanagawa, Japan
    • 1237.6.81116 Boehringer Ingelheim Investigational Site
  • Minami-ku, Yokohama, Kanagawa, Japan
    • 1237.6.81118 Boehringer Ingelheim Investigational Site
  • Mitaka, Tokyo, Japan
    • 1237.6.81112 Boehringer Ingelheim Investigational Site
  • Mito, Ibaraki, Japan
    • 1237.6.81105 Boehringer Ingelheim Investigational Site
  • Naha, Okinawa, Japan
    • 1237.6.81142 Boehringer Ingelheim Investigational Site
  • Nishi-ku, Kobe, Hyogo, Japan
    • 1237.6.81131 Boehringer Ingelheim Investigational Site
  • Obihiro, Hokkaido, Japan
    • 1237.6.81104 Boehringer Ingelheim Investigational Site
  • Okinawa, Okinawa, Japan
    • 1237.6.81141 Boehringer Ingelheim Investigational Site
  • Ota-ku, Tokyo, Japan
    • 1237.6.81110 Boehringer Ingelheim Investigational Site
  • Sakaide, Kagawa, Japan
    • 1237.6.81138 Boehringer Ingelheim Investigational Site
  • Sapporo, Hokkaido, Japan
    • 1237.6.81103 Boehringer Ingelheim Investigational Site
  • Shimajiri-gun, Okinawa, Japan
    • 1237.6.81140 Boehringer Ingelheim Investigational Site
  • Shimajiri-gun, Okinawa, Japan
    • 1237.6.81144 Boehringer Ingelheim Investigational Site
  • Shinjuku-ku, Tokyo, Japan
    • 1237.6.81111 Boehringer Ingelheim Investigational Site
  • Shinjuku-ku, Tokyo, Japan
    • 1237.6.81145 Boehringer Ingelheim Investigational Site
  • Soka, Saitama, Japan
    • 1237.6.81107 Boehringer Ingelheim Investigational Site
  • Takarazuka, Hyogo, Japan
    • 1237.6.81133 Boehringer Ingelheim Investigational Site
  • Takayama, Gifu, Japan
    • 1237.6.81122 Boehringer Ingelheim Investigational Site
  • Tomigusuku, Okinawa, Japan
    • 1237.6.81143 Boehringer Ingelheim Investigational Site
  • Toyonaka, Osaka, Japan
    • 1237.6.81128 Boehringer Ingelheim Investigational Site
  • Uji, Kyoto, Japan
    • 1237.6.81124 Boehringer Ingelheim Investigational Site
  • Yabu, Hyogo, Japan
    • 1237.6.81130 Boehringer Ingelheim Investigational Site
  • Yao, Osaka, Japan
    • 1237.6.81129 Boehringer Ingelheim Investigational Site
  • Yokosuka, Kanagawa, Japan
    • 1237.6.81119 Boehringer Ingelheim Investigational Site
• Norway
  • Elverum, Norway
    • 1237.6.47005 Boehringer Ingelheim Investigational Site
  • Hønefoss, Norway
    • 1237.6.47001 Boehringer Ingelheim Investigational Site
  • Kløfta, Norway
    • 1237.6.47002 Boehringer Ingelheim Investigational Site
  • Lierskogen, Norway
    • 1237.6.47004 Boehringer Ingelheim Investigational Site
  • Oslo, Norway
    • 1237.6.47003 Boehringer Ingelheim Investigational Site
  • SKI, Norway
    • 1237.6.47007 Boehringer Ingelheim Investigational Site
  • Svelvik, Norway
    • 1237.6.47008 Boehringer Ingelheim Investigational Site
• Romania
  • Arad, Romania
    • 1237.6.40004 Boehringer Ingelheim Investigational Site
  • Arad, Romania
    • 1237.6.40005 Boehringer Ingelheim Investigational Site
  • Bucharest, Romania
    • 1237.6.40001 Boehringer Ingelheim Investigational Site
  • Bucuresti, Romania
    • 1237.6.40002 Boehringer Ingelheim Investigational Site
  • Cluj, Romania
    • 1237.6.40003 Boehringer Ingelheim Investigational Site
• Russian Federation
  • Moscow, Russian Federation
    • 1237.6.07004 Boehringer Ingelheim Investigational Site
  • Moscow, Russian Federation
    • 1237.6.07005 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 1237.6.07002 Boehringer Ingelheim Investigational Site
  • St. Petersburg, Russian Federation
    • 1237.6.07003 Boehringer Ingelheim Investigational Site
  • Yaroslavl, Russian Federation
    • 1237.6.07001 Boehringer Ingelheim Investigational Site
• Serbia
  • Belgrade, Serbia
    • 1237.6.38103 Boehringer Ingelheim Investigational Site
  • Belgrade, Serbia
    • 1237.6.38104 Boehringer Ingelheim Investigational Site
  • Belgrade, Serbia
    • 1237.6.38105 Boehringer Ingelheim Investigational Site
  • Kragujevac, Serbia
    • 1237.6.38102 Boehringer Ingelheim Investigational Site
  • Nis, Serbia
    • 1237.6.38101 Boehringer Ingelheim Investigational Site
• Slovakia
  • Bardejov, Slovakia
    • 1237.6.42101 Boehringer Ingelheim Investigational Site
  • Bojnice, Slovakia
    • 1237.6.42102 Boehringer Ingelheim Investigational Site
  • Kosice, Slovakia
    • 1237.6.42104 Boehringer Ingelheim Investigational Site
  • Nitra, Slovakia
    • 1237.6.42107 Boehringer Ingelheim Investigational Site
  • Spisska Nova Ves, Slovakia
    • 1237.6.42103 Boehringer Ingelheim Investigational Site
  • Zilina, Slovakia
    • 1237.6.42106 Boehringer Ingelheim Investigational Site
• South Africa
  • Bellville, South Africa
    • 1237.6.27002 Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • 1237.6.27001 Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • 1237.6.27003 Boehringer Ingelheim Investigational Site
  • Cape Town, South Africa
    • 1237.6.27004 Boehringer Ingelheim Investigational Site
  • Pretoria, South Africa
    • 1237.6.27005 Boehringer Ingelheim Investigational Site
• Spain
  • Badalona (Barcelona), Spain
    • 1237.6.34008 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1237.6.34003 Boehringer Ingelheim Investigational Site
  • Barcelona, Spain
    • 1237.6.34009 Boehringer Ingelheim Investigational Site
  • Hospitalet de Llobregat, Spain
    • 1237.6.34001 Boehringer Ingelheim Investigational Site
  • Mérida, Spain
    • 1237.6.34002 Boehringer Ingelheim Investigational Site
  • Pozuelo de Alarcón, Spain
    • 1237.6.34005 Boehringer Ingelheim Investigational Site
  • San Juan de Alicante, Spain
    • 1237.6.34004 Boehringer Ingelheim Investigational Site
  • Vic (Barcelona), Spain
    • 1237.6.34006 Boehringer Ingelheim Investigational Site
• Sweden
  • Boden, Sweden
    • 1237.6.46003 Boehringer Ingelheim Investigational Site
  • Göteborg, Sweden
    • 1237.6.46002 Boehringer Ingelheim Investigational Site
  • Härnösand, Sweden
    • 1237.6.46006 Boehringer Ingelheim Investigational Site
  • Höllviken, Sweden
    • 1237.6.46005 Boehringer Ingelheim Investigational Site
  • Lund, Sweden
    • 1237.6.46001 Boehringer Ingelheim Investigational Site
  • Stockholm, Sweden
    • 1237.6.46004 Boehringer Ingelheim Investigational Site
  • Uddevalla, Sweden
    • 1237.6.46007 Boehringer Ingelheim Investigational Site
• Taiwan
  • Kaohsiung, Taiwan
    • 1237.6.88608 Boehringer Ingelheim Investigational Site
  • Kaohsiung City, Taiwan
    • 1237.6.88607 Boehringer Ingelheim Investigational Site
  • New Taipei City, Taiwan
    • 1237.6.88602 Boehringer Ingelheim Investigational Site
  • Taichung, Taiwan
    • 1237.6.88604 Boehringer Ingelheim Investigational Site
  • Tainan, Taiwan
    • 1237.6.88605 Boehringer Ingelheim Investigational Site
  • Taipei, Taiwan
    • 1237.6.88601 Boehringer Ingelheim Investigational Site
  • Taoyuan County, Taiwan
    • 1237.6.88603 Boehringer Ingelheim Investigational Site
• Turkey
  • Ankara, Turkey
    • 1237.6.90105 Boehringer Ingelheim Investigational Site
  • Denizli, Turkey
    • 1237.6.90103 Boehringer Ingelheim Investigational Site
  • Istanbul, Turkey
    • 1237.6.90104 Boehringer Ingelheim Investigational Site
  • Izmir, Turkey
    • 1237.6.90101 Boehringer Ingelheim Investigational Site
  • Izmir, Turkey
    • 1237.6.90102 Boehringer Ingelheim Investigational Site
• United Kingdom
  • Blackpool, United Kingdom
    • 1237.6.44002 Boehringer Ingelheim Investigational Site
  • Blackpool, United Kingdom
    • 1237.6.44009 Boehringer Ingelheim Investigational Site
  • Bristol, United Kingdom
    • 1237.6.44007 Boehringer Ingelheim Investigational Site
  • Chertsey, United Kingdom
    • 1237.6.44010 Boehringer Ingelheim Investigational Site
  • Fleetwood, United Kingdom
    • 1237.6.44011 Boehringer Ingelheim Investigational Site
  • Manchester, United Kingdom
    • 1237.6.44001 Boehringer Ingelheim Investigational Site
  • Midsomer Norton, United Kingdom
    • 1237.6.44008 Boehringer Ingelheim Investigational Site
• United States
  • California
    • Greer, California, United States
      • 1237.6.01106 Boehringer Ingelheim Investigational Site
  • Colorado
    • Fort Collins, Colorado, United States
      • 1237.6.01120 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Danbury, Connecticut, United States
      • 1237.6.01131 Boehringer Ingelheim Investigational Site
    • Waterbury, Connecticut, United States
      • 1237.6.01117 Boehringer Ingelheim Investigational Site
  • Florida
    • Deland, Florida, United States
      • 1237.6.01118 Boehringer Ingelheim Investigational Site
    • Tampa, Florida, United States
      • 1237.6.01126 Boehringer Ingelheim Investigational Site
    • Winter Park, Florida, United States
      • 1237.6.01109 Boehringer Ingelheim Investigational Site
  • Georgia
    • Atlanta, Georgia, United States
      • 1237.6.01134 Boehringer Ingelheim Investigational Site
  • Idaho
    • Couer d'Alene, Idaho, United States
      • 1237.6.01107 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Lafayette, Louisiana, United States
      • 1237.6.01110 Boehringer Ingelheim Investigational Site
  • Maryland
    • Baltimore, Maryland, United States
      • 1237.6.01128 Boehringer Ingelheim Investigational Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States
      • 1237.6.01130 Boehringer Ingelheim Investigational Site
  • Minnesota
    • Minneapolis, Minnesota, United States
      • 1237.6.01104 Boehringer Ingelheim Investigational Site
    • Plymouth, Minnesota, United States
      • 1237.6.01116 Boehringer Ingelheim Investigational Site
  • Missouri
    • St. Louis, Missouri, United States
      • 1237.6.01121 Boehringer Ingelheim Investigational Site
    • St. Louis, Missouri, United States
      • 1237.6.01123 Boehringer Ingelheim Investigational Site
  • Nevada
    • Henderson, Nevada, United States
      • 1237.6.01129 Boehringer Ingelheim Investigational Site
  • New Jersey
    • Marlton, New Jersey, United States
      • 1237.6.01136 Boehringer Ingelheim Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States
      • 1237.6.01108 Boehringer Ingelheim Investigational Site
  • New York
    • Bayside, New York, United States
      • 1237.6.01127 Boehringer Ingelheim Investigational Site
    • Great Neck, New York, United States
      • 1237.6.01139 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States
      • 1237.6.01135 Boehringer Ingelheim Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States
      • 1237.6.01114 Boehringer Ingelheim Investigational Site
    • Columbus, Ohio, United States
      • 1237.6.01102 Boehringer Ingelheim Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States
      • 1237.6.01115 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States
      • 1237.6.01101 Boehringer Ingelheim Investigational Site
  • Rhode Island
    • East Providence, Rhode Island, United States
      • 1237.6.01113 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1237.6.01122 Boehringer Ingelheim Investigational Site
    • Greenville, South Carolina, United States
      • 1237.6.01132 Boehringer Ingelheim Investigational Site
    • Greenville, South Carolina, United States
      • 1237.6.01137 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 1237.6.01111 Boehringer Ingelheim Investigational Site
    • Union, South Carolina, United States
      • 1237.6.01105 Boehringer Ingelheim Investigational Site
  • Texas
    • Killeen, Texas, United States
      • 1237.6.01138 Boehringer Ingelheim Investigational Site
    • McKinney, Texas, United States
      • 1237.6.01124 Boehringer Ingelheim Investigational Site
  • Virginia
    • Richmond, Virginia, United States
      • 1237.6.01112 Boehringer Ingelheim Investigational Site
    • Richmond, Virginia, United States
      • 1237.6.01133 Boehringer Ingelheim Investigational Site
  • Washington
    • Spokane, Washington, United States
      • 1237.6.01125 Boehringer Ingelheim Investigational Site
    • Tacoma, Washington, United States
      • 1237.6.01103 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

1. Diagnosis of chronic obstructive pulmonary disease.
2. Relatively stable airway obstruction with post FEV1< 80% predicted normal and post FEV1/FVC <70%.
3. Male or female patients, 40 years of age or older.
4. Smoking history of more than 10 pack years.

Exclusion criteria:

1. Significant disease other than COPD
2. Clinically relevant abnormal lab values.
3. History of asthma.
4. Diagnosis of thyrotoxicosis
5. Diagnosis of paroxysmal tachycardia
6. History of myocardial infarction within 1 year of screening visit
7. Unstable or life-threatening cardiac arrhythmia.
8. Hospitalization for heart failure within the past year.
9. Known active tuberculosis.
10. Malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years
11. History of life-threatening pulmonary obstruction.
12. History of cystic fibrosis.
13. Clinically evident bronchiectasis.
14. History of significant alcohol or drug abuse.
15. Thoracotomy with pulmonary resection
16. Oral ß-adrenergics.
17. Oral corticosteroid medication at unstable doses
18. Regular use of daytime oxygen therapy for more than one hour per day
19. Pulmonary rehabilitation program in the six weeks prior to the screening visit
20. Investigational drug within one month or six half lives (whichever is greater) prior to screening visit
21. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA
22. Pregnant or nursing women.
23. Women of childbearing potential not using a highly effective method of birth control
24. Patients who are unable to comply with pulmonary medication restrictions

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tiotropium+olodaterol low dose FDC; Once daily 2 puffs solution for inhalation Respimat	Device: Respimat; Respimat inhaler; Drug: tiotropium + olodaterol; fixed dose combination
Experimental: tiotropium+olodaterol high dose FDC; Once daily 2 puffs solution for inhalation Respimat	Device: Respimat; Respimat inhaler; Drug: tiotropium + olodaterol; fixed dose combination
Active Comparator: olodaterol; Once daily 2 puffs solution for inhalation Respimat	Device: Respimat; Respimat inhaler; Drug: olodaterol; one dose only
Active Comparator: tiotropium low dose; Once daily 2 puffs solution for inhalation Respimat	Device: Respimat; Respimat inhaler; Drug: tiotropium; low dose or high dose
Active Comparator: tiotropium high dose; Once daily 2 puffs solution for inhalation Respimat	Device: Respimat; Respimat inhaler; Drug: tiotropium; low dose or high dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169	FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the MMRM model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169
Trough FEV1 Response on Day 170	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FEV1 measurements performed at 23 h and at 23 h 50 min after inhalation of study medication at the clinic visit on the previous day. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23 h and at 23 h 50 min after inhalation of study medication on Day 170
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).	The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 169

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	Mahler Transitional Dyspnoea Index (TDI) focal score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274) is the key secondary endpoint. The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 169
FEV1 AUC(0-3h) Response on Day 1	FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment
FEV1 AUC(0-3h) Response on Day 85	FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85
FEV1 AUC(0-3h) Response on Day 365	FEV1 AUC(0-3h) was calculated as the area under the FEV1- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FEV1 AUC(0-3h) response was defined as FEV1 AUC(0-3h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365
Trough FEV1 Response on Day 15	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15
Trough FEV1 Response on Day 43	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43
Trough FEV1 Response on Day 85	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 85
Trough FEV1 Response on Day 169	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1hr and 10 min pre-dose on day 169
Trough FEV1 Response on Day 365	Trough FEV1 was defined as the FEV1 value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FEV1 response was defined as trough FEV1 minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose of randomised treatment at Day1. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 1 hr and 10 min pre-dose on day 365
Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1	FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on the first day of randomized treatment
Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 85	FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC.Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 85 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 85
Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 169	FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 169
Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 365	FVC AUC(0-3h) was calculated as the area under the FVC- time curve from 0 to 3 h post-dose using the trapezoidal rule, divided by the duration (3 h) to report in litres. FVC AUC(0-3h) response was defined as FVC AUC(0-3h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 365 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h post-dose on Day 365
Trough FVC Response on Day 15	Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 15
Trough FVC Response on Day 43	Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 10 min pre-dose on day 43
Trough FVC Response on Day 85	Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85
Trough FVC Response on Day 170	Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours) and was calculated as the mean of the 2 FVC measurements performed at 23h and at 23h 50 min after inhalation of study medication at the clinic visit on the previous day. Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted means (SE) were obtained from fitting an MMRM including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and at 23h and at 23h 50 min after inhalation of study medication on day 170
Trough FVC Response on Day 365	Trough FVC was defined as the FVC value at the end of the dosing interval (24 hours), calculated as the mean of the pre-dose measurements. Trough FVC response was defined as trough FVC minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures (MMRM) model in each treatment group. The adjusted means (SE) were obtained from fitting an Mixed effect model repeated measures (MMRM) including fixed effects of treatment, planned test day, treatment-by-test day interaction, baseline and baseline-by-test day interaction, patient as random effect, and spatial power covariance structure for within-patient errors and Kenward-Roger approximation for denominator degrees of freedom.	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 365
FEV1 AUC(0-12h) Response in Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	FEV1 AUC(0-12h) was calculated as the area under the FEV1- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FEV1 AUC(0-12h) response was defined as FEV1 AUC(0-12h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169
FEV1 AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	FEV1 AUC(0-24h) was calculated as the area under the FEV1- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FEV1 AUC(0-24h) response was defined as FEV1 AUC(0-24h) minus baseline FEV1. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169
FVC AUC(0-12h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	FVC AUC(0-12h) was calculated as the area under the FVC- time curve from 0 to 12 h post-dose using the trapezoidal rule, divided by the duration (12 h) to report in litres. FVC AUC(0-12h) response was defined as FVC AUC(0-12h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h post-dose on Day 169
FVC AUC(0-24h) Response in Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	FVC AUC(0-24h) was calculated as the area under the FVC- time curve from 0 to 24 h post-dose using the trapezoidal rule, divided by the duration (24 h) to report in litres. FVC AUC(0-24h) response was defined as FVC AUC(0-24h) minus baseline FVC. Baseline was defined as the mean of the 2 pre-dose measurements performed 1 h and 10 min prior to administration of the first dose at visit 2 (day 1). The adjusted mean (SE) were obtained from fitting an ANCOVA model with categorical effect of treatment and baseline as covariate. Number of participants analyzed are the number of patients contributing to the ANCOVA model in each treatment group.	1 hour (h) and 10 minutes (min) prior to dose to on the first day of randomized treatment and on Day 169 and 5 min, 15 min, 30 min, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 12 h, 23 h, 23 h and 50 min post-dose on Day 169
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 85
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	The SGRQ is designed to measure health impairment in patients with COPD. It is divided into 2 parts: part 1 produces the symptoms score, and part 2 the activity and impacts scores. A total score is also produced. Each subscale score is the sum of the weights for the items in the subscale as a percent of the sum of the weights for a patient in the worst possible condition. The total score uses the same calculation except that the weights are summed over the entire questionnaire. The individual subscales as well as the total score can range from 0 to 100 with a lower score denoting a better health status. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 365
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	Mahler TDI focal score on Day 43 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 43
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	Mahler TDI focal score on Day 85 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 85
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)	Mahler TDI focal score on Day 365 From the two twin trials, present 1237.6 (NCT01431287) and 1237.5 (NCT01431274). The Mahler Dyspnoea questionnaire is an instrument which measures change from the baseline state The TDI focal score was used to measure the effect of Tio+Olo FDC on patients' dyspnoea after 24 weeks of treatment (Day 169). The focal score is the sum of the subscale scores for Functional Impairment, Magnitude of Effort and Magnitude of Task. Scores for each subscale range from -3 to 3 so that the Focal score ranges from -9 to 9. For all subscale scores and the Focal score a higher value indicates a better outcome. Number of participants analyzed are the number of patients contributing to the mixed effect repeated measures model (MMRM) in each treatment group.	Day 365

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Singh D, Wedzicha JA, Siddiqui S, de la Hoz A, Xue W, Magnussen H, Miravitlles M, Chalmers JD, Calverley PMA. Blood eosinophils as a biomarker of future COPD exacerbation risk: pooled data from 11 clinical trials. Respir Res. 2020 Sep 17;21(1):240. doi: 10.1186/s12931-020-01482-1.
• Buhl R, de la Hoz A, Xue W, Singh D, Ferguson GT. Efficacy of Tiotropium/Olodaterol Compared with Tiotropium as a First-Line Maintenance Treatment in Patients with COPD Who Are Naive to LAMA, LABA and ICS: Pooled Analysis of Four Clinical Trials. Adv Ther. 2020 Oct;37(10):4175-4189. doi: 10.1007/s12325-020-01411-0. Epub 2020 Jul 15.
• Buhl R, Singh D, de la Hoz A, Xue W, Ferguson GT. Benefits of Tiotropium/Olodaterol Compared with Tiotropium in Patients with COPD Receiving only LAMA at Baseline: Pooled Analysis of the TONADO(R) and OTEMTO(R) Studies. Adv Ther. 2020 Aug;37(8):3485-3499. doi: 10.1007/s12325-020-01373-3. Epub 2020 May 27.
• Rabe KF, Chalmers JD, Miravitlles M, Kocks JWH, Tsiligianni I, de la Hoz A, Xue W, Singh D, Ferguson GT, Wedzicha J. Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO(R) Trials. Adv Ther. 2021 Jan;38(1):579-593. doi: 10.1007/s12325-020-01528-2. Epub 2020 Nov 11.
• Andreas S, Bothner U, de la Hoz A, Kloer I, Trampisch M, Alter P. No Influence on Cardiac Arrhythmia or Heart Rate from Long-Term Treatment with Tiotropium/Olodaterol versus Monocomponents by Holter ECG Analysis in Patients with Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1945-1953. doi: 10.2147/COPD.S246350. eCollection 2020.
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Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 8, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 9, 2011

Study Record Updates

• Last Update Posted (Estimate): July 16, 2015
• Last Update Submitted That Met QC Criteria: June 19, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Olodaterol
• Other Study ID Numbers: 1237.6; 2009-010669-22 (EudraCT Number: EudraCT)