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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01533922




Registration number
NCT01533922
Ethics application status
Date submitted
13/02/2012
Date registered
16/02/2012
Date last updated
15/09/2015

Titles & IDs
Public title
Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients
Scientific title
A Randomised, Double-blind, 5 Treatment Arms, 4-period, Incomplete Cross-over Study to Determine the Effect of 6 Weeks Treatment of Orally Inhaled Tiotropium + Olodaterol Fixed Dose Combination (FDC) (2.5 / 5 µg; and 5 / 5 µg) (Delivered by the Respimat® Inhaler) Compared With Tiotropium (5 µg), Olodaterol (5 µg ) and Placebo (Delivered by the Respimat® Inhaler) on Lung Hyperinflation and Exercise Endurance Time During Constant Work Rate Cycle Ergometry in Patients With Chronic Obstructive Pulmonary Disease (COPD) [MORACTO TM 1]
Secondary ID [1] 0 0
2011-004659-37
Secondary ID [2] 0 0
1237.13
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 - Placebo
Treatment: Drugs - Tiotropium
Treatment: Drugs - Olodaterol
Treatment: Drugs - tiotropium + olodaterol
Treatment: Drugs - Tiotropium + Olodaterol
Treatment: Devices - Respimat

Experimental: Tiotropium + olodaterol High dose QD - patient will receive tiotropium 5 mcg + olodaterol 5 mcg in a fixed dose combination once daily

Experimental: Tiotropium + olodaterol Low dose QD - patient will receive tiotropium 2.5 mcg + olodaterol 5 mcg in a fixed dose combination once daily

Active Comparator: Tiotropium 5 mcg QD - patient will receive tiotropium 5 mcg once daily

Active Comparator: Olodaterol 5 mcg QD - patient will receive olodaterol 5 mcg once daily

Placebo Comparator: Placebo QD -


Treatment: Drugs: Placebo
placebo matching tiotropium + olodaterol FDC

Treatment: Drugs: Tiotropium
Tiotropium 5 mcg once daily

Treatment: Drugs: Olodaterol
Olodaterol 5 mcg once daily

Treatment: Drugs: tiotropium + olodaterol
tiotropium + olodaterol 5 mcg once daily

Treatment: Drugs: Tiotropium + Olodaterol
Tiotropium 2.5 mcg + Olodaterol 5 mcg once daily

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
Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap - Inspiratory capacity (IC) at rest before constant work rate cycle ergometry to symptom limitation at 75% maximal work capacity (Wcap).
Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.
The presented means are adjusted means from the MMRM (Mixed Effects Model Repeated Measures) model.
Timepoint [1] 0 0
6 weeks
Primary outcome [2] 0 0
Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap - Endurance time during constant work rate cycle ergometry (CWRCE) to symptom limitation at 75% work capacity (Wcap).
Wcap was defined as the maximum work rate achieved for at least 30 seconds during the incremental cycle ergometry performed at Visit 1.
The presented means are adjusted mean from the MMRM model.
Timepoint [2] 0 0
6 weeks
Secondary outcome [1] 0 0
Slope of the Intensity of Breathing Discomfort During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity - Slope of the intensity of breathing discomfort during Constant Work Rate Cycle Ergometry (CWRCE) to symptom limitation at 75% Work capacity (Wcap). The intensity of breathing discomfort was rated using the modified Borg scale with ratings from 0 (nothing at all) to 10 (maximal).
Slope of breathing discomfort is defined as: (intensity of breathing discomfort at the end of exercise minus intensity of breathing discomfort at rest) / endurance time.
A decrease in slope indicates improvement.
The presented means are adjusted means from MMRM model.
Timepoint [1] 0 0
6 weeks
Secondary outcome [2] 0 0
Forced Expiratory Volume in 1 Second (One Hour Post-dose) - Forced Expiratory Volume in 1 Second (FEV1) (one hour post-dose)
The presented means are adjusted means from MMRM model.
Timepoint [2] 0 0
6 weeks

Eligibility
Key inclusion criteria
Inclusion criteria:

1. All patients must sign an informed consent consistent with ICH-GCP guidelines prior to
participation in the trial, which includes medication washout and restrictions.

2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must
meet the following spirometric criteria:

Patients must have relatively stable airway obstruction with a post-bronchodilator
FEV1 <80% of predicted normal and a post-bronchodilator FEV1/FVC <70% at Visit 1.

3. Male or female patients, between 40 and 75 years of age (inclusive) on day of signing
informed consent.

4. Patients must be current or ex-smokers with a smoking history of more than 10 pack
years.
Minimum age
40 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Patients with a significant disease other than COPD; a significant disease is defined
as a disease which, in the opinion of the investigator, may (i) put the patient at
risk because of participation in the study, (ii) influence the results of the study,
or (iii) cause concern regarding the patient's ability to participate in the study

2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or
urinalysis; all patients with an SGOT >x2 ULN, SGPT >x2 ULN, bilirubin >x2 ULN or
creatinine >x2 ULN will be excluded regardless of clinical condition

3. Patients with a history of asthma. For patients with allergic rhinitis or atopy,
source documentation is required to verify that the patient does not have asthma.

Patients with any of the following conditions:

4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of
ß2-agonists)

5. A diagnosis of paroxysmal tachycardia (>100 beats per minute) (due to the known class
side effect profile of ß2-agonists)

6. A history of myocardial infarction within 1 year of screening visit (Visit 1)

7. Unstable or life-threatening cardiac arrhythmia

8. Hospitalized for heart failure within the past year

9. Known active tuberculosis

10. A malignancy for which patient has undergone resection, radiation therapy or
chemotherapy within last five years (patients with treated basal cell carcinoma are
allowed)

11. A history of life-threatening pulmonary obstruction

12. A history of cystic fibrosis

13. Clinically evident bronchiectasis

14. A history of significant alcohol or drug abuse

15. Any contraindications for exercise testing.

16. Patients who have undergone thoracotomy with pulmonary resection (patients with a
history of thoracotomy for other reasons should be evaluated as per exclusion
criterion No. 1)

17. Patients being treated with any oral ß-adrenergics

18. Patients being treated with oral corticosteroid medication at unstable doses

19. Patients who regularly use daytime oxygen therapy for more than one hour per day and
in the investigator's opinion will be unable to abstain from the use of oxygen therapy
during clinic visits

20. Patients who have completed a pulmonary rehabilitation program in the six weeks prior
to the screening visit or patients who are currently in a pulmonary rehabilitation
program

21. Patients who have a limitation of exercise performance as a result of factors other
than fatigue or exertional dyspnoea, such as arthritis in the leg, angina pectoris or
claudication or morbid obesity.

22. Patients who have taken an investigational drug within one month or six half lives
(whichever is greater) prior to screening visit

23. Patients with known hypersensitivity to ß-adrenergics drugs, anticholinergic drugs,
BAC, EDTA or any other component of the Respimat® inhalation solution delivery system

24. Pregnant or nursing women

25. Women of childbearing potential not using highly effective methods of birth control.

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
Crossover
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)
NSW,SA,VIC
Recruitment hospital [1] 0 0
1237.13.61306 Boehringer Ingelheim Investigational Site - Concord
Recruitment hospital [2] 0 0
1237.13.61301 Boehringer Ingelheim Investigational Site - Daw Park
Recruitment hospital [3] 0 0
1237.13.61305 Boehringer Ingelheim Investigational Site - Toorak Gardens
Recruitment hospital [4] 0 0
1237.13.61304 Boehringer Ingelheim Investigational Site - Footscray
Recruitment hospital [5] 0 0
1237.13.61302 Boehringer Ingelheim Investigational Site - Prahran
Recruitment postcode(s) [1] 0 0
- Concord
Recruitment postcode(s) [2] 0 0
- Daw Park
Recruitment postcode(s) [3] 0 0
- Toorak Gardens
Recruitment postcode(s) [4] 0 0
- Footscray
Recruitment postcode(s) [5] 0 0
- Prahran
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Michigan
Country [4] 0 0
United States of America
State/province [4] 0 0
Pennsylvania
Country [5] 0 0
United States of America
State/province [5] 0 0
South Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Virginia
Country [7] 0 0
Argentina
State/province [7] 0 0
Capital Federal
Country [8] 0 0
Argentina
State/province [8] 0 0
Mar del Plata
Country [9] 0 0
Austria
State/province [9] 0 0
Linz
Country [10] 0 0
Austria
State/province [10] 0 0
Thalheim bei Wels
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussel
Country [12] 0 0
Belgium
State/province [12] 0 0
Edegem
Country [13] 0 0
Belgium
State/province [13] 0 0
Jambes
Country [14] 0 0
Belgium
State/province [14] 0 0
Lanaken
Country [15] 0 0
Belgium
State/province [15] 0 0
Leuven
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
Canada
State/province [17] 0 0
Saskatchewan
Country [18] 0 0
Chile
State/province [18] 0 0
Chile
Country [19] 0 0
Chile
State/province [19] 0 0
Santiago de Chile
Country [20] 0 0
Germany
State/province [20] 0 0
Berlin
Country [21] 0 0
Germany
State/province [21] 0 0
Dortmund
Country [22] 0 0
Germany
State/province [22] 0 0
Frankfurt
Country [23] 0 0
Germany
State/province [23] 0 0
Halle
Country [24] 0 0
Germany
State/province [24] 0 0
Hannover
Country [25] 0 0
Germany
State/province [25] 0 0
Lübeck
Country [26] 0 0
Italy
State/province [26] 0 0
Genova
Country [27] 0 0
Italy
State/province [27] 0 0
Parma
Country [28] 0 0
Italy
State/province [28] 0 0
Pavia
Country [29] 0 0
Italy
State/province [29] 0 0
Pavullo Nel Frignano (mo)
Country [30] 0 0
Italy
State/province [30] 0 0
Pisa
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Italy
State/province [32] 0 0
Sesto S. Giovanni (mi)
Country [33] 0 0
Italy
State/province [33] 0 0
Trieste
Country [34] 0 0
New Zealand
State/province [34] 0 0
Christchurch
Country [35] 0 0
New Zealand
State/province [35] 0 0
Greenlane East Auckland NZ

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this trial is to investigate the effect of 6 weeks treatment with
tiotropium + olodaterol fixed dose combination inhalation solution on lung hyperinflation and
exercise tolerance in patients with COPD
Trial website
https://clinicaltrials.gov/show/NCT01533922
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

Summary results
Other publications