Clinical trial NCT01533922: Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients
Official 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]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Disease, Chronic Obstructive
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-02-16
Enrollment: 295
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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


Eligibility 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.

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.

Primary outcomes:
measure: Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
timeFrame: 6 weeks
measure: Endurance Time During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
timeFrame: 6 weeks
Secondary outcomes:
measure: Slope of the Intensity of Breathing Discomfort During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity
timeFrame: 6 weeks
measure: Forced Expiratory Volume in 1 Second (One Hour Post-dose)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Torrance
country: United States
facility: 1237.13.01302 Boehringer Ingelheim Investigational Site
state: California
city: Hartford
country: United States
facility: 1237.13.01308 Boehringer Ingelheim Investigational Site
state: Connecticut
city: Livonia
country: United States
facility: 1237.13.01304 Boehringer Ingelheim Investigational Site
state: Michigan
city: Pittsburgh
country: United States
facility: 1237.13.01307 Boehringer Ingelheim Investigational Site
state: Pennsylvania
city: Easley
country: United States
facility: 1237.13.01305 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Greenville
country: United States
facility: 1237.13.01301 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1237.13.01303 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Richmond
country: United States
facility: 1237.13.01306 Boehringer Ingelheim Investigational Site
state: Virginia
city: Capital Federal
country: Argentina
facility: 1237.13.54301 Boehringer Ingelheim Investigational Site
city: Mar del Plata
country: Argentina
facility: 1237.13.54302 Boehringer Ingelheim Investigational Site
city: Concord
country: Australia
facility: 1237.13.61306 Boehringer Ingelheim Investigational Site
state: New South Wales
city: Daw Park
country: Australia
facility: 1237.13.61301 Boehringer Ingelheim Investigational Site
state: South Australia
city: Toorak Gardens
country: Australia
facility: 1237.13.61305 Boehringer Ingelheim Investigational Site
state: South Australia
city: Footscray
country: Australia
facility: 1237.13.61304 Boehringer Ingelheim Investigational Site
state: Victoria
city: Prahran
country: Australia
facility: 1237.13.61302 Boehringer Ingelheim Investigational Site
state: Victoria
city: Linz
country: Austria
facility: 1237.13.43303 Boehringer Ingelheim Investigational Site
city: Thalheim bei Wels
country: Austria
facility: 1237.13.43301 Boehringer Ingelheim Investigational Site
city: Brussel
country: Belgium
facility: 1237.13.32302 Boehringer Ingelheim Investigational Site
city: Edegem
country: Belgium
facility: 1237.13.32303 Boehringer Ingelheim Investigational Site
city: Jambes
country: Belgium
facility: 1237.13.32305 Boehringer Ingelheim Investigational Site
city: Lanaken
country: Belgium
facility: 1237.13.32304 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1237.13.32301 Boehringer Ingelheim Investigational Site
city: Hamilton
country: Canada
facility: 1237.13.11302 Boehringer Ingelheim Investigational Site
state: Ontario
city: Kingston
country: Canada
facility: 1237.13.11303 Boehringer Ingelheim Investigational Site
state: Ontario
city: Saskatoon
country: Canada
facility: 1237.13.11304 Boehringer Ingelheim Investigational Site
state: Saskatchewan
city: Chile
country: Chile
facility: 1237.13.56301 Boehringer Ingelheim Investigational Site
city: Santiago de Chile
country: Chile
facility: 1237.13.56302 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1237.13.49302 Boehringer Ingelheim Investigational Site
city: Dortmund
country: Germany
facility: 1237.13.49307 Boehringer Ingelheim Investigational Site
city: Frankfurt
country: Germany
facility: 1237.13.49304 Boehringer Ingelheim Investigational Site
city: Halle
country: Germany
facility: 1237.13.49301 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1237.13.49303 Boehringer Ingelheim Investigational Site
city: Lübeck
country: Germany
facility: 1237.13.49305 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1237.13.39302 Boehringer Ingelheim Investigational Site
city: Parma
country: Italy
facility: 1237.13.39304 Boehringer Ingelheim Investigational Site
city: Pavia
country: Italy
facility: 1237.13.39303 Boehringer Ingelheim Investigational Site
city: Pavullo Nel Frignano (mo)
country: Italy
facility: 1237.13.39305 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1237.13.39301 Boehringer Ingelheim Investigational Site
city: Pisa
country: Italy
facility: 1237.13.39312 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1237.13.39310 Boehringer Ingelheim Investigational Site
city: Sesto S. Giovanni (mi)
country: Italy
facility: 1237.13.39308 Boehringer Ingelheim Investigational Site
city: Trieste
country: Italy
facility: 1237.13.39306 Boehringer Ingelheim Investigational Site
city: Christchurch
country: New Zealand
facility: 1237.13.64302 Boehringer Ingelheim Investigational Site
city: Greenlane East Auckland NZ
country: New Zealand
facility: 1237.13.64301 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: O'Donnell DE, Casaburi R, Frith P, Kirsten A, De Sousa D, Hamilton A, Xue W, Maltais F. Effects of combined tiotropium/olodaterol on inspiratory capacity and exercise endurance in COPD. Eur Respir J. 2017 Apr 19;49(4):1601348. doi: 10.1183/13993003.01348-2016. Print 2017 Apr.