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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01431287




Registration number
NCT01431287
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 2]
Secondary ID [1] 0 0
2009-010669-22
Secondary ID [2] 0 0
1237.6
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
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 + olodaterol
Treatment: Drugs - tiotropium
Treatment: Drugs - tiotropium
Treatment: Drugs - olodaterol
Treatment: Devices - Respimat

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

Experimental: tiotropium+olodaterol low 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 + olodaterol
fixed dose combination

Treatment: Drugs: tiotropium
low dose or high dose

Treatment: Drugs: tiotropium
low dose or high dose

Treatment: Drugs: olodaterol
one dose only

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 1237.6 (NCT01431287) and 1237.5 (NCT01431274).
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1hr 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 1hr 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
Forced Vital Capacity (FVC) 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
Forced Vital Capacity (FVC) 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
Forced Vital Capacity (FVC) 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
Forced Vital Capacity (FVC) 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 23h and at 23h 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 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)
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 Sub-set of Patients With 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 Sub-set of Patients With 12-hour PFTs on Day 169 From Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 12-hour PFTs on Day 169 From the Two Twin Trials, Present 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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 1237.6 (NCT01431287) and 1237.5 (NCT01431274)
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
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Innsbruck
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Fukui, Fukui
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Fukuyama, Hiroshima
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Hachioji, Tokyo
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Himeji, Hyogo
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Japan
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Hitachi, Ibaraki
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Iizuka, Fukuoka
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Iwamizawa, Hokkaido
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Kamakura, Kanagawa
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Japan
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Kanazawa, Ishikawa
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Japan
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Kanazawa, Yokohama, Kanagawa
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Kashiwa, Chiba
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Kawasaki-ku, Kawasaki, Kanagawa
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Kita-ku, Okayama, Okayama
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Kita-ku, Sakai, Osaka
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Kita-ku, Sapporo, Hokkaido
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Japan
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Kurashiki, Okayama
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Japan
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Minami-ku, Yokohama, Kanagawa
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Japan
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Mitaka, Tokyo
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Japan
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Mito, Ibaraki
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Japan
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Naha, Okinawa
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Japan
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Nishi-ku, Kobe, Hyogo
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Japan
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Obihiro, Hokkaido
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Japan
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Okinawa, Okinawa
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Japan
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Ota-ku, Tokyo
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Japan
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Sakaide, Kagawa
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Japan
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Sapporo, Hokkaido
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Japan
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Shimajiri-gun, Okinawa
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Japan
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Shinjuku-ku, Tokyo
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Japan
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Soka, Saitama
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Japan
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Takarazuka, Hyogo
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Japan
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Takayama, Gifu
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Japan
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Tomigusuku, Okinawa
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Japan
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Toyonaka, Osaka
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Japan
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Uji, Kyoto
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Japan
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Yabu, Hyogo
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Japan
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Yao, Osaka
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Japan
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Yokosuka, Kanagawa
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Norway
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Elverum
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Norway
State/province [141] 0 0
Hønefoss
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SKI
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Arad
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State/province [148] 0 0
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State/province [149] 0 0
Bucuresti
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Cluj
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Moscow
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State/province [152] 0 0
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State/province [153] 0 0
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State/province [161] 0 0
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State/province [196] 0 0
Midsomer Norton

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

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.