Effect on Exercise Endurance and Lung Hyperinflation of Tiotropium + Olodaterol in COPD Patients

Pulmonary Disease, Chronic Obstructive Clinical Trial

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]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01533922
• Other study ID #: 1237.13
• Secondary ID: 2011-004659-37
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2012
• Last updated: August 12, 2015
• Start date: March 2012
• Est. completion date: November 2013

Study information

• Verified date: August 2015
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Human Research Ethics CommitteeAustria: Austrian Medicines and Medical Devices AgencyBelgium: The Federal Public Service (FPS) Health, Food Chain Safety and EnvironmentCanada: Health CanadaChile: Instituto de Salud Pública de ChileGermany: Federal Institute for Drugs and Medical DevicesItaly: Ethics CommitteeNew Zealand: MedsafeUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 295
• Est. completion date: November 2013
• Est. primary completion date: November 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Disease
• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• Placebo
placebo matching tiotropium + olodaterol FDC
• Tiotropium
Tiotropium 5 mcg once daily
• Olodaterol
Olodaterol 5 mcg once daily
• tiotropium + olodaterol
tiotropium + olodaterol 5 mcg once daily
• Tiotropium + Olodaterol
Tiotropium 2.5 mcg + Olodaterol 5 mcg once daily

Device:
• Respimat
Respimat inhaler

Locations

Country	Name	City	State
Argentina	1237.13.54301 Boehringer Ingelheim Investigational Site	Capital Federal
Argentina	1237.13.54302 Boehringer Ingelheim Investigational Site	Mar del Plata
Australia	1237.13.61306 Boehringer Ingelheim Investigational Site	Concord	New South Wales
Australia	1237.13.61301 Boehringer Ingelheim Investigational Site	Daw Park	South Australia
Australia	1237.13.61304 Boehringer Ingelheim Investigational Site	Footscray	Victoria
Australia	1237.13.61302 Boehringer Ingelheim Investigational Site	Prahran	Victoria
Australia	1237.13.61305 Boehringer Ingelheim Investigational Site	Toorak Gardens	South Australia
Austria	1237.13.43303 Boehringer Ingelheim Investigational Site	Linz
Austria	1237.13.43301 Boehringer Ingelheim Investigational Site	Thalheim bei Wels
Belgium	1237.13.32302 Boehringer Ingelheim Investigational Site	Brussel
Belgium	1237.13.32303 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1237.13.32305 Boehringer Ingelheim Investigational Site	Jambes
Belgium	1237.13.32304 Boehringer Ingelheim Investigational Site	Lanaken
Belgium	1237.13.32301 Boehringer Ingelheim Investigational Site	Leuven
Canada	1237.13.11302 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1237.13.11303 Boehringer Ingelheim Investigational Site	Kingston	Ontario
Canada	1237.13.11304 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan
Chile	1237.13.56301 Boehringer Ingelheim Investigational Site	Chile
Chile	1237.13.56302 Boehringer Ingelheim Investigational Site	Santiago de Chile
Germany	1237.13.49302 Boehringer Ingelheim Investigational Site	Berlin
Germany	1237.13.49307 Boehringer Ingelheim Investigational Site	Dortmund
Germany	1237.13.49304 Boehringer Ingelheim Investigational Site	Frankfurt
Germany	1237.13.49301 Boehringer Ingelheim Investigational Site	Halle
Germany	1237.13.49303 Boehringer Ingelheim Investigational Site	Hannover
Germany	1237.13.49305 Boehringer Ingelheim Investigational Site	Lübeck
Italy	1237.13.39302 Boehringer Ingelheim Investigational Site	Genova
Italy	1237.13.39304 Boehringer Ingelheim Investigational Site	Parma
Italy	1237.13.39303 Boehringer Ingelheim Investigational Site	Pavia
Italy	1237.13.39305 Boehringer Ingelheim Investigational Site	Pavullo Nel Frignano (mo)
Italy	1237.13.39301 Boehringer Ingelheim Investigational Site	Pisa
Italy	1237.13.39312 Boehringer Ingelheim Investigational Site	Pisa
Italy	1237.13.39310 Boehringer Ingelheim Investigational Site	Roma
Italy	1237.13.39308 Boehringer Ingelheim Investigational Site	Sesto S. Giovanni (mi)
Italy	1237.13.39306 Boehringer Ingelheim Investigational Site	Trieste
New Zealand	1237.13.64302 Boehringer Ingelheim Investigational Site	Christchurch
New Zealand	1237.13.64301 Boehringer Ingelheim Investigational Site	Greenlane East Auckland NZ
United States	1237.13.01305 Boehringer Ingelheim Investigational Site	Easley	South Carolina
United States	1237.13.01301 Boehringer Ingelheim Investigational Site	Greenville	South Carolina
United States	1237.13.01308 Boehringer Ingelheim Investigational Site	Hartford	Connecticut
United States	1237.13.01304 Boehringer Ingelheim Investigational Site	Livonia	Michigan
United States	1237.13.01307 Boehringer Ingelheim Investigational Site	Pittsburgh	Pennsylvania
United States	1237.13.01306 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1237.13.01303 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina
United States	1237.13.01302 Boehringer Ingelheim Investigational Site	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  Germany,  Italy,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 weeks	No
Primary	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.	6 weeks	No
Secondary	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.	6 weeks	No
Secondary	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.	6 weeks	No

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