Clinical trial NCT01533935: 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 2]
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: 291
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% Work Capacity
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 (Borg Scale) During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap
timeFrame: 6 weeks
measure: FEV1 (1 Hour Post-dose)
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 1237.14.01404 Boehringer Ingelheim Investigational Site
state: Arizona
city: Austell
country: United States
facility: 1237.14.01414 Boehringer Ingelheim Investigational Site
state: Georgia
city: Baltimore
country: United States
facility: 1237.14.01417 Boehringer Ingelheim Investigational Site
state: Maryland
city: Rochester
country: United States
facility: 1237.14.01418 Boehringer Ingelheim Investigational Site
state: Minnesota
city: St. Charles
country: United States
facility: 1237.14.01408 Boehringer Ingelheim Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: 1237.14.01409 Boehringer Ingelheim Investigational Site
state: North Carolina
city: Greenville
country: United States
facility: 1237.14.01407 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: 1237.14.01403 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Union
country: United States
facility: 1237.14.01401 Boehringer Ingelheim Investigational Site
state: South Carolina
city: Dallas
country: United States
facility: 1237.14.01412 Boehringer Ingelheim Investigational Site
state: Texas
city: Seattle
country: United States
facility: 1237.14.01410 Boehringer Ingelheim Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: 1237.14.54402 Boehringer Ingelheim Investigational Site
city: Mendoza
country: Argentina
facility: 1237.14.54401 Boehringer Ingelheim Investigational Site
city: Grieskirchen
country: Austria
facility: 1237.14.43402 Boehringer Ingelheim Investigational Site
city: Neumarkt am Wallersee
country: Austria
facility: 1237.14.43401 Boehringer Ingelheim Investigational Site
city: Vancouver
country: Canada
facility: 1237.14.11404 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: 1237.14.11403 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1237.14.11402 Boehringer Ingelheim Investigational Site
state: Quebec
city: Ste-Foy
country: Canada
facility: 1237.14.11401 Boehringer Ingelheim Investigational Site
state: Quebec
city: Bamberg
country: Germany
facility: 1237.14.49406 Boehringer Ingelheim Investigational Site
city: Bochum
country: Germany
facility: 1237.14.49404 Boehringer Ingelheim Investigational Site
city: Großhansdorf
country: Germany
facility: 1237.14.49401 Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: 1237.14.49405 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1237.14.49403 Boehringer Ingelheim Investigational Site
city: Kiel
country: Germany
facility: 1237.14.49402 Boehringer Ingelheim Investigational Site
city: Heerlen
country: Netherlands
facility: 1237.14.31001 Boehringer Ingelheim Investigational Site
city: Hoofddorp
country: Netherlands
facility: 1237.14.31005 Boehringer Ingelheim Investigational Site
city: Hoorn
country: Netherlands
facility: 1237.14.31004 Boehringer Ingelheim Investigational Site
city: Leeuwarden
country: Netherlands
facility: 1237.14.31006 Medisch Centrum Leeuwarden
city: Leiden
country: Netherlands
facility: 1237.14.31007 Boehringer Ingelheim Investigational Site
city: Moscow
country: Russian Federation
facility: 1237.14.70401 Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: 1237.14.70402 Boehringer Ingelheim Investigational Site
city: Lund
country: Sweden
facility: 1237.14.46001 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.