Clinical trial NCT01431287: Tiotropium +Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)
Official title: 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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-09-09
Enrollment: 2539
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169
timeFrame: 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
measure: Trough FEV1 Response on Day 170
timeFrame: 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
measure: Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274).
timeFrame: Day 169
Secondary outcomes:
measure: Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 169
measure: FEV1 AUC(0-3h) Response on Day 1
timeFrame: 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
measure: FEV1 AUC(0-3h) Response on Day 85
timeFrame: 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
measure: FEV1 AUC(0-3h) Response on Day 365
timeFrame: 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
measure: Trough FEV1 Response on Day 15
timeFrame: 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
measure: Trough FEV1 Response on Day 43
timeFrame: 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
measure: Trough FEV1 Response on Day 85
timeFrame: 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
measure: Trough FEV1 Response on Day 169
timeFrame: 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
measure: Trough FEV1 Response on Day 365
timeFrame: 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
measure: Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 1
timeFrame: 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
measure: Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 85
timeFrame: 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
measure: Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 169
timeFrame: 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
measure: Forced Vital Capacity (FVC) AUC(0-3h) Response on Day 365
timeFrame: 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
measure: Trough FVC Response on Day 15
timeFrame: 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
measure: Trough FVC Response on Day 43
timeFrame: 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
measure: Trough FVC Response on Day 85
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85
measure: Trough FVC Response on Day 170
timeFrame: 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
measure: Trough FVC Response on Day 365
timeFrame: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 365
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 85
measure: Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 365
measure: Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 43
measure: Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 85
measure: Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
timeFrame: Day 365
Other outcomes:
Locations:
city: Greer
country: United States
facility: 1237.6.01106 Boehringer Ingelheim Investigational Site
state: California
city: Fort Collins
country: United States
facility: 1237.6.01120 Boehringer Ingelheim Investigational Site
state: Colorado
city: Danbury
country: United States
facility: 1237.6.01131 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: 1237.6.01117 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Deland
country: United States
facility: 1237.6.01118 Boehringer Ingelheim Investigational Site
state: Florida
city: Tampa
country: United States
facility: 1237.6.01126 Boehringer Ingelheim Investigational Site
state: Florida
city: Winter Park
country: United States
facility: 1237.6.01109 Boehringer Ingelheim Investigational Site
state: Florida
city: Atlanta
country: United States
facility: 1237.6.01134 Boehringer Ingelheim Investigational Site
state: Georgia
city: Couer d'Alene
country: United States
facility: 1237.6.01107 Boehringer Ingelheim Investigational Site
state: Idaho
city: Lafayette
country: United States
facility: 1237.6.01110 Boehringer Ingelheim Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: 1237.6.01128 Boehringer Ingelheim Investigational Site
state: Maryland
city: North Dartmouth
country: United States
facility: 1237.6.01130 Boehringer Ingelheim Investigational Site
state: Massachusetts
city: Minneapolis
country: United States
facility: 1237.6.01104 Boehringer Ingelheim Investigational Site
state: Minnesota
city: Plymouth
country: United States
facility: 1237.6.01116 Boehringer Ingelheim Investigational Site
state: Minnesota
city: St. Louis
country: United States
facility: 1237.6.01121 Boehringer Ingelheim Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: 1237.6.01123 Boehringer Ingelheim Investigational Site
state: Missouri
city: Henderson
country: United States
facility: 1237.6.01129 Boehringer Ingelheim Investigational Site
state: Nevada
city: Marlton
country: United States
facility: 1237.6.01136 Boehringer Ingelheim Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: 1237.6.01108 Boehringer Ingelheim Investigational Site
state: New Mexico
city: Bayside
country: United States
facility: 1237.6.01127 Boehringer Ingelheim Investigational Site
state: New York
city: Great Neck
country: United States
facility: 1237.6.01139 Boehringer Ingelheim Investigational Site
state: New York
city: Charlotte
country: United States
facility: 1237.6.01135 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: 1237.6.01114 Boehringer Ingelheim Investigational Site
state: Ohio
city: Columbus
country: United States
facility: 1237.6.01102 Boehringer Ingelheim Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: 1237.6.01115 Boehringer Ingelheim Investigational Site
state: Oklahoma
city: Philadelphia
country: United States
facility: 1237.6.01101 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: East Providence
country: United States
facility: 1237.6.01113 Boehringer Ingelheim Investigational Site
state: Rhode Island
city: Charleston
country: United States
facility: 1237.6.01122 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1237.6.01132 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1237.6.01137 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1237.6.01111 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Union
country: United States
facility: 1237.6.01105 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Killeen
country: United States
facility: 1237.6.01138 Boehringer Ingelheim Investigational Site
state: Texas
city: McKinney
country: United States
facility: 1237.6.01124 Boehringer Ingelheim Investigational Site
state: Texas
city: Richmond
country: United States
facility: 1237.6.01112 Boehringer Ingelheim Investigational Site
state: Virginia
city: Richmond
country: United States
facility: 1237.6.01133 Boehringer Ingelheim Investigational Site
state: Virginia
city: Spokane
country: United States
facility: 1237.6.01125 Boehringer Ingelheim Investigational Site
state: Washington
city: Tacoma
country: United States
facility: 1237.6.01103 Boehringer Ingelheim Investigational Site
state: Washington
city: Feldbach
country: Austria
facility: 1237.6.43006 Boehringer Ingelheim Investigational Site
city: Gänserndorf
country: Austria
facility: 1237.6.43005 Boehringer Ingelheim Investigational Site
city: Innsbruck
country: Austria
facility: 1237.6.43002 Boehringer Ingelheim Investigational Site
city: Leoben
country: Austria
facility: 1237.6.43004 Boehringer Ingelheim Investigational Site
city: Linz
country: Austria
facility: 1237.6.43001 Boehringer Ingelheim Investigational Site
city: Salzburg
country: Austria
facility: 1237.6.43003 Boehringer Ingelheim Investigational Site
city: Brussel
country: Belgium
facility: 1237.6.32007 Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: 1237.6.32005 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1237.6.32004 Boehringer Ingelheim Investigational Site
city: Jambes
country: Belgium
facility: 1237.6.32002 Boehringer Ingelheim Investigational Site
city: Lebbeke
country: Belgium
facility: 1237.6.32009 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1237.6.32001 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1237.6.32006 Boehringer Ingelheim Investigational Site
city: Oostende
country: Belgium
facility: 1237.6.32008 Boehringer Ingelheim Investigational Site
city: Turnhout
country: Belgium
facility: 1237.6.32010 Boehringer Ingelheim Investigational Site
city: Botucatu
country: Brazil
facility: 1237.6.55013 Boehringer Ingelheim Investigational Site
city: Florianopolis
country: Brazil
facility: 1237.6.55010 Boehringer Ingelheim Investigational Site
city: Passo Fundo
country: Brazil
facility: 1237.6.55012 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1237.6.55001 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1237.6.55002 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1237.6.55003 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1237.6.55005 Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: 1237.6.55009 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 1237.6.55006 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 1237.6.55007 Boehringer Ingelheim Investigational Site
city: Sao Paulo
country: Brazil
facility: 1237.6.55011 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1237.6.02109 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1237.6.02111 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Moncton
country: Canada
facility: 1237.6.02106 Boehringer Ingelheim Investigational Site
state: New Brunswick
city: Courtice
country: Canada
facility: 1237.6.02110 Boehringer Ingelheim Investigational Site
state: Ontario
city: Downsview
country: Canada
facility: 1237.6.02101 Boehringer Ingelheim Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: 1237.6.02112 Boehringer Ingelheim Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: 1237.6.02103 Boehringer Ingelheim Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: 1237.6.02102 Boehringer Ingelheim Investigational Site
state: Ontario
city: Point Claire
country: Canada
facility: 1237.6.02104 Boehringer Ingelheim Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: 1237.6.02105 Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: 1237.6.02108 Boehringer Ingelheim Investigational Site
state: Quebec
city: Baotou
country: China
facility: 1237.6.86117 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1237.6.86102 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1237.6.86104 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1237.6.86105 Boehringer Ingelheim Investigational Site
city: Changsha
country: China
facility: 1237.6.86115 Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: 1237.6.86110 Boehringer Ingelheim Investigational Site
city: Chongqing
country: China
facility: 1237.6.86111 Boehringer Ingelheim Investigational Site
city: Haikou
country: China
facility: 1237.6.86109 Boehringer Ingelheim Investigational Site
city: Hangzhou
country: China
facility: 1237.6.86108 Boehringer Ingelheim Investigational Site
city: Hohhot
country: China
facility: 1237.6.86116 Boehringer Ingelheim Investigational Site
city: Jinan
country: China
facility: 1237.6.86114 Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: 1237.6.86106 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1237.6.86101 Boehringer Ingelheim Investigational Site
city: Shenyang
country: China
facility: 1237.6.86113 Boehringer Ingelheim Investigational Site
city: Suzhou
country: China
facility: 1237.6.86107 Boehringer Ingelheim Investigational Site
city: Xi'An
country: China
facility: 1237.6.86112 Boehringer Ingelheim Investigational Site
city: Bogota DC
country: Colombia
facility: 1237.6.57001 Boehringer Ingelheim Investigational Site
city: Bogota DC
country: Colombia
facility: 1237.6.57003 Boehringer Ingelheim Investigational Site
city: Bogota DC
country: Colombia
facility: 1237.6.57007 Boehringer Ingelheim Investigational Site
city: Bogota
country: Colombia
facility: 1237.6.57008 Boehringer Ingelheim Investigational Site
city: Cali
country: Colombia
facility: 1237.6.57006 Boehringer Ingelheim Investigational Site
city: Floridablanca
country: Colombia
facility: 1237.6.57004 Boehringer Ingelheim Investigational Site
city: Petrinja
country: Croatia
facility: 1237.6.38503 Boehringer Ingelheim Investigational Site
city: Rijeka
country: Croatia
facility: 1237.6.38504 Boehringer Ingelheim Investigational Site
city: Zadar
country: Croatia
facility: 1237.6.38502 Boehringer Ingelheim Investigational Site
city: Zagreb
country: Croatia
facility: 1237.6.38501 Boehringer Ingelheim Investigational Site
city: Aschaffenburg
country: Germany
facility: 1237.6.49022 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.6.49017 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1237.6.49026 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1237.6.49027 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1237.6.49025 Boehringer Ingelheim Investigational Site
city: Halle
country: Germany
facility: 1237.6.49016 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1237.6.49024 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1237.6.49021 Boehringer Ingelheim Investigational Site
city: Leipzig
country: Germany
facility: 1237.6.49019 Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: 1237.6.49028 Boehringer Ingelheim Investigational Site
city: Rodgau/Dudenhofen
country: Germany
facility: 1237.6.49018 Boehringer Ingelheim Investigational Site
city: Schwerin
country: Germany
facility: 1237.6.49020 Boehringer Ingelheim Investigational Site
city: Teuchern
country: Germany
facility: 1237.6.49023 Boehringer Ingelheim Investigational Site
city: Debrecen
country: Hungary
facility: 1237.6.36001 Boehringer Ingelheim Investigational Site
city: Gödöllö
country: Hungary
facility: 1237.6.36004 Boehringer Ingelheim Investigational Site
city: Pecs
country: Hungary
facility: 1237.6.36005 Boehringer Ingelheim Investigational Site
city: Sopron
country: Hungary
facility: 1237.6.36003 Boehringer Ingelheim Investigational Site
city: Szeged
country: Hungary
facility: 1237.6.36002 Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: 1237.6.91003 Boehringer Ingelheim Investigational Site
city: Coimbatore
country: India
facility: 1237.6.91011 Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: 1237.6.91004 Boehringer Ingelheim Investigational Site
city: Kolkatta
country: India
facility: 1237.6.91002 Boehringer Ingelheim Investigational Site
city: Maharastra
country: India
facility: 1237.6.91007 Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: 1237.6.91006 Boehringer Ingelheim Investigational Site
city: Nashik, Maharashtra
country: India
facility: 1237.6.91009 Boehringer Ingelheim Investigational Site
city: Pune
country: India
facility: 1237.6.91008 Boehringer Ingelheim Investigational Site
city: County Limerick
country: Ireland
facility: 1237.6.35304 Boehringer Ingelheim Investigational Site
city: Dublin 24
country: Ireland
facility: 1237.6.35303 Boehringer Ingelheim Investigational Site
city: Dublin 4
country: Ireland
facility: 1237.6.35301 Boehringer Ingelheim Investigational Site
city: Abeno-ku, Osaka, Osaka
country: Japan
facility: 1237.6.81127 Boehringer Ingelheim Investigational Site
city: Aoi-ku, Shizuoka, Shizuoka
country: Japan
facility: 1237.6.81123 Boehringer Ingelheim Investigational Site
city: Chuo-ku, Kobe, Hyogo
country: Japan
facility: 1237.6.81132 Boehringer Ingelheim Investigational Site
city: Fukui, Fukui
country: Japan
facility: 1237.6.81121 Boehringer Ingelheim Investigational Site
city: Fukuyama, Hiroshima
country: Japan
facility: 1237.6.81137 Boehringer Ingelheim Investigational Site
city: Hachioji, Tokyo
country: Japan
facility: 1237.6.81109 Boehringer Ingelheim Investigational Site
city: Himeji, Hyogo
country: Japan
facility: 1237.6.81134 Boehringer Ingelheim Investigational Site
city: Hitachi, Ibaraki
country: Japan
facility: 1237.6.81106 Boehringer Ingelheim Investigational Site
city: Iizuka, Fukuoka
country: Japan
facility: 1237.6.81139 Boehringer Ingelheim Investigational Site
city: Iwamizawa, Hokkaido
country: Japan
facility: 1237.6.81102 Boehringer Ingelheim Investigational Site
city: Kamakura, Kanagawa
country: Japan
facility: 1237.6.81117 Boehringer Ingelheim Investigational Site
city: Kanazawa, Ishikawa
country: Japan
facility: 1237.6.81120 Boehringer Ingelheim Investigational Site
city: Kanazawa, Yokohama, Kanagawa
country: Japan
facility: 1237.6.81113 Boehringer Ingelheim Investigational Site
city: Kashiwa, Chiba
country: Japan
facility: 1237.6.81108 Boehringer Ingelheim Investigational Site
city: Kawasaki-ku, Kawasaki, Kanagawa
country: Japan
facility: 1237.6.81114 Boehringer Ingelheim Investigational Site
city: Kita-ku, Okayama, Okayama
country: Japan
facility: 1237.6.81135 Boehringer Ingelheim Investigational Site
city: Kita-ku, Sakai, Osaka
country: Japan
facility: 1237.6.81126 Boehringer Ingelheim Investigational Site
city: Kita-ku, Sapporo, Hokkaido
country: Japan
facility: 1237.6.81101 Boehringer Ingelheim Investigational Site
city: Kurashiki, Okayama
country: Japan
facility: 1237.6.81136 Boehringer Ingelheim Investigational Site
city: Minami-ku, Yokohama, Kanagawa
country: Japan
facility: 1237.6.81116 Boehringer Ingelheim Investigational Site
city: Minami-ku, Yokohama, Kanagawa
country: Japan
facility: 1237.6.81118 Boehringer Ingelheim Investigational Site
city: Mitaka, Tokyo
country: Japan
facility: 1237.6.81112 Boehringer Ingelheim Investigational Site
city: Mito, Ibaraki
country: Japan
facility: 1237.6.81105 Boehringer Ingelheim Investigational Site
city: Naha, Okinawa
country: Japan
facility: 1237.6.81142 Boehringer Ingelheim Investigational Site
city: Nishi-ku, Kobe, Hyogo
country: Japan
facility: 1237.6.81131 Boehringer Ingelheim Investigational Site
city: Obihiro, Hokkaido
country: Japan
facility: 1237.6.81104 Boehringer Ingelheim Investigational Site
city: Okinawa, Okinawa
country: Japan
facility: 1237.6.81141 Boehringer Ingelheim Investigational Site
city: Ota-ku, Tokyo
country: Japan
facility: 1237.6.81110 Boehringer Ingelheim Investigational Site
city: Sakaide, Kagawa
country: Japan
facility: 1237.6.81138 Boehringer Ingelheim Investigational Site
city: Sapporo, Hokkaido
country: Japan
facility: 1237.6.81103 Boehringer Ingelheim Investigational Site
city: Shimajiri-gun, Okinawa
country: Japan
facility: 1237.6.81140 Boehringer Ingelheim Investigational Site
city: Shimajiri-gun, Okinawa
country: Japan
facility: 1237.6.81144 Boehringer Ingelheim Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: 1237.6.81111 Boehringer Ingelheim Investigational Site
city: Shinjuku-ku, Tokyo
country: Japan
facility: 1237.6.81145 Boehringer Ingelheim Investigational Site
city: Soka, Saitama
country: Japan
facility: 1237.6.81107 Boehringer Ingelheim Investigational Site
city: Takarazuka, Hyogo
country: Japan
facility: 1237.6.81133 Boehringer Ingelheim Investigational Site
city: Takayama, Gifu
country: Japan
facility: 1237.6.81122 Boehringer Ingelheim Investigational Site
city: Tomigusuku, Okinawa
country: Japan
facility: 1237.6.81143 Boehringer Ingelheim Investigational Site
city: Toyonaka, Osaka
country: Japan
facility: 1237.6.81128 Boehringer Ingelheim Investigational Site
city: Uji, Kyoto
country: Japan
facility: 1237.6.81124 Boehringer Ingelheim Investigational Site
city: Yabu, Hyogo
country: Japan
facility: 1237.6.81130 Boehringer Ingelheim Investigational Site
city: Yao, Osaka
country: Japan
facility: 1237.6.81129 Boehringer Ingelheim Investigational Site
city: Yokosuka, Kanagawa
country: Japan
facility: 1237.6.81119 Boehringer Ingelheim Investigational Site
city: Elverum
country: Norway
facility: 1237.6.47005 Boehringer Ingelheim Investigational Site
city: Hønefoss
country: Norway
facility: 1237.6.47001 Boehringer Ingelheim Investigational Site
city: Kløfta
country: Norway
facility: 1237.6.47002 Boehringer Ingelheim Investigational Site
city: Lierskogen
country: Norway
facility: 1237.6.47004 Boehringer Ingelheim Investigational Site
city: Oslo
country: Norway
facility: 1237.6.47003 Boehringer Ingelheim Investigational Site
city: SKI
country: Norway
facility: 1237.6.47007 Boehringer Ingelheim Investigational Site
city: Svelvik
country: Norway
facility: 1237.6.47008 Boehringer Ingelheim Investigational Site
city: Arad
country: Romania
facility: 1237.6.40004 Boehringer Ingelheim Investigational Site
city: Arad
country: Romania
facility: 1237.6.40005 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1237.6.40001 Boehringer Ingelheim Investigational Site
city: Bucuresti
country: Romania
facility: 1237.6.40002 Boehringer Ingelheim Investigational Site
city: Cluj
country: Romania
facility: 1237.6.40003 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1237.6.07004 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1237.6.07005 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1237.6.07002 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1237.6.07003 Boehringer Ingelheim Investigational Site
city: Yaroslavl
country: Russian Federation
facility: 1237.6.07001 Boehringer Ingelheim Investigational Site
city: Belgrade
country: Serbia
facility: 1237.6.38103 Boehringer Ingelheim Investigational Site
city: Belgrade
country: Serbia
facility: 1237.6.38104 Boehringer Ingelheim Investigational Site
city: Belgrade
country: Serbia
facility: 1237.6.38105 Boehringer Ingelheim Investigational Site
city: Kragujevac
country: Serbia
facility: 1237.6.38102 Boehringer Ingelheim Investigational Site
city: Nis
country: Serbia
facility: 1237.6.38101 Boehringer Ingelheim Investigational Site
city: Bardejov
country: Slovakia
facility: 1237.6.42101 Boehringer Ingelheim Investigational Site
city: Bojnice
country: Slovakia
facility: 1237.6.42102 Boehringer Ingelheim Investigational Site
city: Kosice
country: Slovakia
facility: 1237.6.42104 Boehringer Ingelheim Investigational Site
city: Nitra
country: Slovakia
facility: 1237.6.42107 Boehringer Ingelheim Investigational Site
city: Spisska Nova Ves
country: Slovakia
facility: 1237.6.42103 Boehringer Ingelheim Investigational Site
city: Zilina
country: Slovakia
facility: 1237.6.42106 Boehringer Ingelheim Investigational Site
city: Bellville
country: South Africa
facility: 1237.6.27002 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1237.6.27001 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1237.6.27003 Boehringer Ingelheim Investigational Site
city: Cape Town
country: South Africa
facility: 1237.6.27004 Boehringer Ingelheim Investigational Site
city: Pretoria
country: South Africa
facility: 1237.6.27005 Boehringer Ingelheim Investigational Site
city: Badalona (Barcelona)
country: Spain
facility: 1237.6.34008 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1237.6.34003 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1237.6.34009 Boehringer Ingelheim Investigational Site
city: Hospitalet de Llobregat
country: Spain
facility: 1237.6.34001 Boehringer Ingelheim Investigational Site
city: Mérida
country: Spain
facility: 1237.6.34002 Boehringer Ingelheim Investigational Site
city: Pozuelo de Alarcón
country: Spain
facility: 1237.6.34005 Boehringer Ingelheim Investigational Site
city: San Juan de Alicante
country: Spain
facility: 1237.6.34004 Boehringer Ingelheim Investigational Site
city: Vic (Barcelona)
country: Spain
facility: 1237.6.34006 Boehringer Ingelheim Investigational Site
city: Boden
country: Sweden
facility: 1237.6.46003 Boehringer Ingelheim Investigational Site
city: Göteborg
country: Sweden
facility: 1237.6.46002 Boehringer Ingelheim Investigational Site
city: Härnösand
country: Sweden
facility: 1237.6.46006 Boehringer Ingelheim Investigational Site
city: Höllviken
country: Sweden
facility: 1237.6.46005 Boehringer Ingelheim Investigational Site
city: Lund
country: Sweden
facility: 1237.6.46001 Boehringer Ingelheim Investigational Site
city: Stockholm
country: Sweden
facility: 1237.6.46004 Boehringer Ingelheim Investigational Site
city: Uddevalla
country: Sweden
facility: 1237.6.46007 Boehringer Ingelheim Investigational Site
city: Kaohsiung City
country: Taiwan
facility: 1237.6.88607 Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: 1237.6.88608 Boehringer Ingelheim Investigational Site
city: New Taipei City
country: Taiwan
facility: 1237.6.88602 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1237.6.88604 Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: 1237.6.88605 Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: 1237.6.88601 Boehringer Ingelheim Investigational Site
city: Taoyuan County
country: Taiwan
facility: 1237.6.88603 Boehringer Ingelheim Investigational Site
city: Ankara
country: Turkey
facility: 1237.6.90105 Boehringer Ingelheim Investigational Site
city: Denizli
country: Turkey
facility: 1237.6.90103 Boehringer Ingelheim Investigational Site
city: Istanbul
country: Turkey
facility: 1237.6.90104 Boehringer Ingelheim Investigational Site
city: Izmir
country: Turkey
facility: 1237.6.90101 Boehringer Ingelheim Investigational Site
city: Izmir
country: Turkey
facility: 1237.6.90102 Boehringer Ingelheim Investigational Site
city: Blackpool
country: United Kingdom
facility: 1237.6.44002 Boehringer Ingelheim Investigational Site
city: Blackpool
country: United Kingdom
facility: 1237.6.44009 Boehringer Ingelheim Investigational Site
city: Bristol
country: United Kingdom
facility: 1237.6.44007 Boehringer Ingelheim Investigational Site
city: Chertsey
country: United Kingdom
facility: 1237.6.44010 Boehringer Ingelheim Investigational Site
city: Fleetwood
country: United Kingdom
facility: 1237.6.44011 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1237.6.44001 Boehringer Ingelheim Investigational Site
city: Midsomer Norton
country: United Kingdom
facility: 1237.6.44008 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Andreas S, McGarvey L, Bothner U, Trampisch M, de la Hoz A, Flezar M, Buhl R, Alter P. Absence of Adverse Effects of Tiotropium/Olodaterol Compared with the Monocomponents on Long-Term Heart Rate and Blood Pressure in Patients with Moderate-to-Very-Severe COPD. Int J Chron Obstruct Pulmon Dis. 2020 Aug 10;15:1935-1944. doi: 10.2147/COPD.S246348. eCollection 2020.
citation: Wedzicha JA, Buhl R, Singh D, Vogelmeier CF, de la Hoz A, Xue W, Anzueto A, Calverley PMA. Tiotropium/Olodaterol Decreases Exacerbation Rates Compared with Tiotropium in a Range of Patients with COPD: Pooled Analysis of the TONADO(R)/DYNAGITO(R) Trials. Adv Ther. 2020 Oct;37(10):4266-4279. doi: 10.1007/s12325-020-01438-3. Epub 2020 Aug 10.
citation: 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.
citation: 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.
citation: Ferguson GT, Buhl R, Bothner U, Hoz A, Voss F, Anzueto A, Calverley PMA. Safety of tiotropium/olodaterol in chronic obstructive pulmonary disease: pooled analysis of three large, 52-week, randomized clinical trials. Respir Med. 2018 Oct;143:67-73. doi: 10.1016/j.rmed.2018.08.012. Epub 2018 Aug 28.
citation: Maltais F, Buhl R, Koch A, Amatto VC, Reid J, Gronke L, Bothner U, Voss F, McGarvey L, Ferguson GT. beta-Blockers in COPD: A Cohort Study From the TONADO Research Program. Chest. 2018 Jun;153(6):1315-1325. doi: 10.1016/j.chest.2018.01.008. Epub 2018 Jan 31.
citation: Buhl R, Magder S, Bothner U, Tetzlaff K, Voss F, Loaiza L, Vogelmeier CF, McGarvey L. Long-term general and cardiovascular safety of tiotropium/olodaterol in patients with moderate to very severe chronic obstructive pulmonary disease. Respir Med. 2017 Jan;122:58-66. doi: 10.1016/j.rmed.2016.11.011. Epub 2016 Nov 14.
citation: Ferguson GT, Flezar M, Korn S, Korducki L, Gronke L, Abrahams R, Buhl R. Efficacy of Tiotropium + Olodaterol in Patients with Chronic Obstructive Pulmonary Disease by Initial Disease Severity and Treatment Intensity: A Post Hoc Analysis. Adv Ther. 2015 Jun;32(6):523-36. doi: 10.1007/s12325-015-0218-0. Epub 2015 Jun 26.
citation: Buhl R, Maltais F, Abrahams R, Bjermer L, Derom E, Ferguson G, Flezar M, Hebert J, McGarvey L, Pizzichini E, Reid J, Veale A, Gronke L, Hamilton A, Korducki L, Tetzlaff K, Waitere-Wijker S, Watz H, Bateman E. Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4). Eur Respir J. 2015 Apr;45(4):969-79. doi: 10.1183/09031936.00136014. Epub 2015 Jan 8.