Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01431274




Registration number
NCT01431274
Ethics application status
Date submitted
8/09/2011
Date registered
9/09/2011
Date last updated
16/07/2015

Titles & IDs
Public title
Tiotropium+Olodaterol Fixed Dose Combination (FDC) Versus Tiotropium and Olodaterol in Chronic Obstructive Pulmonary Disease (COPD)
Scientific 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 1]
Secondary ID [1] 0 0
2009-010668-40
Secondary ID [2] 0 0
1237.5
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tiotropium + olodaterol
Treatment: Drugs - tiotropium
Treatment: Drugs - olodaterol
Treatment: Drugs - tiotropium
Treatment: Drugs - tiotropium + olodaterol
Treatment: Devices - Respimat

Experimental: tiotropium+olodaterol low dose FDC - Once daily 2 puffs solution for inhalation Respimat

Experimental: tiotropium+olodaterol high dose FDC - Once daily 2 puffs solution for inhalation Respimat

Active comparator: olodaterol - Once daily 2 puffs solution for inhalation Respimat

Active comparator: tiotropium low dose - Once daily 2 puffs solution for inhalation Respimat

Active comparator: tiotropium high dose - Once daily 2 puffs solution for inhalation Respimat


Treatment: Drugs: tiotropium + olodaterol
fixed dose combination

Treatment: Drugs: tiotropium
low dose

Treatment: Drugs: olodaterol
one dose only

Treatment: Drugs: tiotropium
high dose

Treatment: Drugs: tiotropium + olodaterol
fixed dose combination

Treatment: Devices: Respimat
Respimat inhaler
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Devices
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Forced Expiratory Volume in One Second (FEV1) Area Under the Curve (AUC) (0-3h) Response on Day 169.
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Trough FEV1 Response on Day 170.
Timepoint [2] 0 0
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
Primary outcome [3] 0 0
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [3] 0 0
Day 169
Secondary outcome [1] 0 0
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [1] 0 0
Day 169
Secondary outcome [2] 0 0
FEV1 AUC(0-3h) Response on Day 1
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
FEV1 AUC(0-3h) Response on Day 85
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
FEV1 AUC(0-3h) Response on Day 365
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Trough FEV1 Response on Day 15.
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
Trough FEV1 Response on Day 43
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Trough FEV1 Response on Day 85
Timepoint [7] 0 0
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 85.
Secondary outcome [8] 0 0
Trough FEV1 Response on Day 169
Timepoint [8] 0 0
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 169
Secondary outcome [9] 0 0
Trough FEV1 Response on Day 365
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 1
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 85
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 169
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
FVC (Forced Vital Capacity) AUC(0-3h) Response on Day 365
Timepoint [13] 0 0
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.
Secondary outcome [14] 0 0
Trough FVC Response on Day 15.
Timepoint [14] 0 0
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
Secondary outcome [15] 0 0
Trough FVC Response on Day 43.
Timepoint [15] 0 0
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
Secondary outcome [16] 0 0
Trough FVC Response on Day 85.
Timepoint [16] 0 0
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on day 85
Secondary outcome [17] 0 0
Trough FVC Response on Day 170.
Timepoint [17] 0 0
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
Secondary outcome [18] 0 0
Trough FVC Response on Day 365.
Timepoint [18] 0 0
1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and on Day 365.
Secondary outcome [19] 0 0
FEV1 AUC(0-12h) Response in the Sub-set of Patients With 12-hour Pulmonary Function Test (PFT) on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [19] 0 0
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.
Secondary outcome [20] 0 0
FEV1 AUC(0-24h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [20] 0 0
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.
Secondary outcome [21] 0 0
FVC AUC(0-12h) Response in the Sub-set of Patients With 12-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [21] 0 0
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.
Secondary outcome [22] 0 0
FVC AUC(0-24h) Response in Sub-set of Patients With 24-h PFTs on Day 169 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [22] 0 0
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.
Secondary outcome [23] 0 0
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [23] 0 0
Day 85
Secondary outcome [24] 0 0
Saint George's Respiratory Questionnaire (SGRQ) Total Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [24] 0 0
Day 365
Secondary outcome [25] 0 0
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 43 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [25] 0 0
Day 43
Secondary outcome [26] 0 0
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 85 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [26] 0 0
Day 85
Secondary outcome [27] 0 0
Mahler Transitional Dyspnoea Index (TDI) Focal Score on Day 365 From the Two Twin Trials, Present 1237.5 (NCT01431274) and 1237.6 (NCT01431287)
Timepoint [27] 0 0
Day 365

Eligibility
Key inclusion 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.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2011
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/09/2013
Sample size
Target
Accrual to date
Final
2624
Recruitment in Australia
Recruitment state(s)
SA,VIC
Recruitment hospital [1] 0 0
1237.5.61001 Boehringer Ingelheim Investigational Site - Toorak Gardens
Recruitment hospital [2] 0 0
1237.5.61002 Boehringer Ingelheim Investigational Site - Woodville
Recruitment hospital [3] 0 0
1237.5.61004 Boehringer Ingelheim Investigational Site - Frankston
Recruitment postcode(s) [1] 0 0
- Toorak Gardens
Recruitment postcode(s) [2] 0 0
- Woodville
Recruitment postcode(s) [3] 0 0
- Frankston
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Louisiana
Country [7] 0 0
United States of America
State/province [7] 0 0
Maine
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Nebraska
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Oklahoma
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Rhode Island
Country [17] 0 0
United States of America
State/province [17] 0 0
South Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Virginia
Country [20] 0 0
United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
State/province [21] 0 0
West Virginia
Country [22] 0 0
Argentina
State/province [22] 0 0
Buenos Aires
Country [23] 0 0
Argentina
State/province [23] 0 0
Caba
Country [24] 0 0
Argentina
State/province [24] 0 0
Capital Federal
Country [25] 0 0
Argentina
State/province [25] 0 0
Cuidad Autonoma de Buenos Airess A
Country [26] 0 0
Argentina
State/province [26] 0 0
Mar del Plata
Country [27] 0 0
Argentina
State/province [27] 0 0
Mendoza
Country [28] 0 0
Argentina
State/province [28] 0 0
Monte Grande
Country [29] 0 0
Argentina
State/province [29] 0 0
Quilmes
Country [30] 0 0
Argentina
State/province [30] 0 0
Rosario
Country [31] 0 0
Argentina
State/province [31] 0 0
San Miguel de Tucuman
Country [32] 0 0
Argentina
State/province [32] 0 0
San Miguel de Tucuma
Country [33] 0 0
Bulgaria
State/province [33] 0 0
Plovdiv
Country [34] 0 0
Bulgaria
State/province [34] 0 0
Rousse
Country [35] 0 0
Bulgaria
State/province [35] 0 0
Shumen
Country [36] 0 0
Bulgaria
State/province [36] 0 0
Sofia
Country [37] 0 0
Bulgaria
State/province [37] 0 0
Troyan
Country [38] 0 0
Bulgaria
State/province [38] 0 0
Veliko Tarnovo
Country [39] 0 0
Canada
State/province [39] 0 0
Alberta
Country [40] 0 0
Canada
State/province [40] 0 0
British Columbia
Country [41] 0 0
Canada
State/province [41] 0 0
Manitoba
Country [42] 0 0
Canada
State/province [42] 0 0
Ontario
Country [43] 0 0
Canada
State/province [43] 0 0
Quebec
Country [44] 0 0
Canada
State/province [44] 0 0
Saskatchewan
Country [45] 0 0
China
State/province [45] 0 0
Beijing
Country [46] 0 0
China
State/province [46] 0 0
Changsha
Country [47] 0 0
China
State/province [47] 0 0
Foshan
Country [48] 0 0
China
State/province [48] 0 0
Guangzhou
Country [49] 0 0
China
State/province [49] 0 0
Nan Ning
Country [50] 0 0
China
State/province [50] 0 0
Shanghai
Country [51] 0 0
China
State/province [51] 0 0
Shenyang
Country [52] 0 0
China
State/province [52] 0 0
Wuhan
Country [53] 0 0
China
State/province [53] 0 0
Xi'An
Country [54] 0 0
China
State/province [54] 0 0
Yangzhou
Country [55] 0 0
China
State/province [55] 0 0
Yinchuan
Country [56] 0 0
Czech Republic
State/province [56] 0 0
Beroun
Country [57] 0 0
Czech Republic
State/province [57] 0 0
Cvikov
Country [58] 0 0
Czech Republic
State/province [58] 0 0
Praha 6
Country [59] 0 0
Czech Republic
State/province [59] 0 0
Rokycany
Country [60] 0 0
Czech Republic
State/province [60] 0 0
Znojmo
Country [61] 0 0
Denmark
State/province [61] 0 0
Aalborg
Country [62] 0 0
Denmark
State/province [62] 0 0
Hvidovre
Country [63] 0 0
Denmark
State/province [63] 0 0
Kolding
Country [64] 0 0
Denmark
State/province [64] 0 0
København NV
Country [65] 0 0
Denmark
State/province [65] 0 0
Næstved
Country [66] 0 0
Denmark
State/province [66] 0 0
Odense C
Country [67] 0 0
Denmark
State/province [67] 0 0
Roskilde
Country [68] 0 0
Denmark
State/province [68] 0 0
Silkeborg
Country [69] 0 0
Denmark
State/province [69] 0 0
Sønderborg
Country [70] 0 0
Denmark
State/province [70] 0 0
Vaerløse
Country [71] 0 0
Estonia
State/province [71] 0 0
Tallin
Country [72] 0 0
Estonia
State/province [72] 0 0
Tartu
Country [73] 0 0
Finland
State/province [73] 0 0
Helsinki
Country [74] 0 0
Finland
State/province [74] 0 0
Pori
Country [75] 0 0
Finland
State/province [75] 0 0
Turku
Country [76] 0 0
France
State/province [76] 0 0
Bethune Cedex
Country [77] 0 0
France
State/province [77] 0 0
Montpellier cedex 5
Country [78] 0 0
France
State/province [78] 0 0
Nantes
Country [79] 0 0
France
State/province [79] 0 0
Nîmes cedex 9
Country [80] 0 0
France
State/province [80] 0 0
Perpignan
Country [81] 0 0
France
State/province [81] 0 0
Saint Pierre Cedex
Country [82] 0 0
France
State/province [82] 0 0
Strasbourg
Country [83] 0 0
Germany
State/province [83] 0 0
Bamberg
Country [84] 0 0
Germany
State/province [84] 0 0
Berlin
Country [85] 0 0
Germany
State/province [85] 0 0
Erfurt
Country [86] 0 0
Germany
State/province [86] 0 0
Hamburg
Country [87] 0 0
Germany
State/province [87] 0 0
Koblenz
Country [88] 0 0
Germany
State/province [88] 0 0
Neu-Isenburg
Country [89] 0 0
Germany
State/province [89] 0 0
Oschersleben
Country [90] 0 0
Germany
State/province [90] 0 0
Rüdersdorf
Country [91] 0 0
Germany
State/province [91] 0 0
Weinheim
Country [92] 0 0
Germany
State/province [92] 0 0
Wiesloch
Country [93] 0 0
Guatemala
State/province [93] 0 0
Guatemala
Country [94] 0 0
Hungary
State/province [94] 0 0
Debrecen
Country [95] 0 0
Hungary
State/province [95] 0 0
Deszk
Country [96] 0 0
Hungary
State/province [96] 0 0
Kapuvar
Country [97] 0 0
Hungary
State/province [97] 0 0
Szombathely
Country [98] 0 0
Hungary
State/province [98] 0 0
Törökbalint
Country [99] 0 0
India
State/province [99] 0 0
Ahmedabad
Country [100] 0 0
India
State/province [100] 0 0
Bangalore
Country [101] 0 0
India
State/province [101] 0 0
Coimbatore
Country [102] 0 0
India
State/province [102] 0 0
Hyderabad
Country [103] 0 0
India
State/province [103] 0 0
Jaipur
Country [104] 0 0
India
State/province [104] 0 0
Mysore
Country [105] 0 0
India
State/province [105] 0 0
Pune
Country [106] 0 0
Italy
State/province [106] 0 0
Cagliari
Country [107] 0 0
Italy
State/province [107] 0 0
Genova
Country [108] 0 0
Italy
State/province [108] 0 0
Montescano (PV)
Country [109] 0 0
Italy
State/province [109] 0 0
Monza
Country [110] 0 0
Italy
State/province [110] 0 0
Parma
Country [111] 0 0
Italy
State/province [111] 0 0
Pisa
Country [112] 0 0
Japan
State/province [112] 0 0
Aoba-ku, Sendai, Miyagi
Country [113] 0 0
Japan
State/province [113] 0 0
Asahikawa, Hokkaido
Country [114] 0 0
Japan
State/province [114] 0 0
Bunkyo-ku, Tokyo
Country [115] 0 0
Japan
State/province [115] 0 0
Chuo-ku, Kumamoto, Kumamoto
Country [116] 0 0
Japan
State/province [116] 0 0
Gifu, Gifu
Country [117] 0 0
Japan
State/province [117] 0 0
Hakata-ku, Fukuoka, Fukuoka
Country [118] 0 0
Japan
State/province [118] 0 0
Hamamatsushi, Shizuoka
Country [119] 0 0
Japan
State/province [119] 0 0
Himeji, Hyogo
Country [120] 0 0
Japan
State/province [120] 0 0
Ikoma, Nara
Country [121] 0 0
Japan
State/province [121] 0 0
Inashiki-gun, Ibaraki
Country [122] 0 0
Japan
State/province [122] 0 0
Itabashi-ku, Tokyo
Country [123] 0 0
Japan
State/province [123] 0 0
Jonan-ku, Fukuoka, Fukuoka
Country [124] 0 0
Japan
State/province [124] 0 0
Kagoshima, Kagoshima,
Country [125] 0 0
Japan
State/province [125] 0 0
Kagoshima, Kagoshima
Country [126] 0 0
Japan
State/province [126] 0 0
Kamogawa, Chiba
Country [127] 0 0
Japan
State/province [127] 0 0
Kishiwada, Osaka
Country [128] 0 0
Japan
State/province [128] 0 0
Kitakyusyu,Fukuoka
Country [129] 0 0
Japan
State/province [129] 0 0
Koga, Fukuoka
Country [130] 0 0
Japan
State/province [130] 0 0
Komaki, Aichi
Country [131] 0 0
Japan
State/province [131] 0 0
Koshi, Kumamoto
Country [132] 0 0
Japan
State/province [132] 0 0
koto-ku, Tokyo
Country [133] 0 0
Japan
State/province [133] 0 0
Kuki, Saitama
Country [134] 0 0
Japan
State/province [134] 0 0
Kure, Hiroshima
Country [135] 0 0
Japan
State/province [135] 0 0
Kurume, Fukuoka
Country [136] 0 0
Japan
State/province [136] 0 0
Matsumoto, Nagano
Country [137] 0 0
Japan
State/province [137] 0 0
Matsusaka, Mie
Country [138] 0 0
Japan
State/province [138] 0 0
Minami-ku. Fukuoka, Fukuoka
Country [139] 0 0
Japan
State/province [139] 0 0
Morioka, Iwate
Country [140] 0 0
Japan
State/province [140] 0 0
Nagoya, Aichi
Country [141] 0 0
Japan
State/province [141] 0 0
Naka-gun, Ibaraki
Country [142] 0 0
Japan
State/province [142] 0 0
Okinawa, Urasoe
Country [143] 0 0
Japan
State/province [143] 0 0
Sayama, Osaka
Country [144] 0 0
Japan
State/province [144] 0 0
Sendai, Miyagi
Country [145] 0 0
Japan
State/province [145] 0 0
Seto, Aichi
Country [146] 0 0
Japan
State/province [146] 0 0
Shinagawa, Tokyo
Country [147] 0 0
Japan
State/province [147] 0 0
Shinjyuku-ku, Tokyo
Country [148] 0 0
Japan
State/province [148] 0 0
Takamatsu, Kagawa
Country [149] 0 0
Japan
State/province [149] 0 0
Wakayama, Wakayama
Country [150] 0 0
Japan
State/province [150] 0 0
Yanagawa-shi, Fukuoka,
Country [151] 0 0
Japan
State/province [151] 0 0
Yokohama, Kanagawa
Country [152] 0 0
Korea, Republic of
State/province [152] 0 0
Bucheon
Country [153] 0 0
Korea, Republic of
State/province [153] 0 0
Daegu
Country [154] 0 0
Korea, Republic of
State/province [154] 0 0
Seoul
Country [155] 0 0
Korea, Republic of
State/province [155] 0 0
Suwon
Country [156] 0 0
Korea, Republic of
State/province [156] 0 0
Wonju
Country [157] 0 0
Mexico
State/province [157] 0 0
Hermosillo
Country [158] 0 0
Mexico
State/province [158] 0 0
Mexico
Country [159] 0 0
Mexico
State/province [159] 0 0
Monterrey
Country [160] 0 0
Mexico
State/province [160] 0 0
Tijuana
Country [161] 0 0
Netherlands
State/province [161] 0 0
Almelo
Country [162] 0 0
Netherlands
State/province [162] 0 0
Breda
Country [163] 0 0
Netherlands
State/province [163] 0 0
Eindhoven
Country [164] 0 0
Netherlands
State/province [164] 0 0
Harderwijk
Country [165] 0 0
Netherlands
State/province [165] 0 0
Heerlen
Country [166] 0 0
Netherlands
State/province [166] 0 0
Hengelo
Country [167] 0 0
Netherlands
State/province [167] 0 0
Hoorn
Country [168] 0 0
Netherlands
State/province [168] 0 0
Nieuwegein
Country [169] 0 0
Netherlands
State/province [169] 0 0
Veldhoven
Country [170] 0 0
Netherlands
State/province [170] 0 0
Zutphen
Country [171] 0 0
New Zealand
State/province [171] 0 0
Dunedin
Country [172] 0 0
New Zealand
State/province [172] 0 0
Greenlane East Auckland NZ
Country [173] 0 0
Portugal
State/province [173] 0 0
Amadora
Country [174] 0 0
Portugal
State/province [174] 0 0
Coimbra
Country [175] 0 0
Portugal
State/province [175] 0 0
Lisboa
Country [176] 0 0
Portugal
State/province [176] 0 0
Porto
Country [177] 0 0
Portugal
State/province [177] 0 0
Vila Nova de Gaia
Country [178] 0 0
Portugal
State/province [178] 0 0
Viseu
Country [179] 0 0
Russian Federation
State/province [179] 0 0
Gatchina (Leningradskaya oblast)
Country [180] 0 0
Russian Federation
State/province [180] 0 0
Kazan
Country [181] 0 0
Russian Federation
State/province [181] 0 0
Moscow
Country [182] 0 0
Russian Federation
State/province [182] 0 0
St. Petersburg
Country [183] 0 0
Slovenia
State/province [183] 0 0
Golnik
Country [184] 0 0
Turkey
State/province [184] 0 0
Istanbul
Country [185] 0 0
Turkey
State/province [185] 0 0
Izmir
Country [186] 0 0
Turkey
State/province [186] 0 0
Izmit
Country [187] 0 0
Turkey
State/province [187] 0 0
Mersin

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
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 Chronic Obstructive Pulmonary Disease (COPD).
Trial website
https://clinicaltrials.gov/study/NCT01431274
Trial related presentations / publications
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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. Erratum In: Eur Respir J. 2015 Jun;45(6):1763. doi: 10.1183/09031936.50136014.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01431274