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 2]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01533935
• Other study ID #: 1237.14
• Secondary ID: 2011-004660-30
• Status: Completed
• Phase: Phase 3
• First received: February 13, 2012
• Last updated: August 12, 2015
• Start date: February 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 MedicaAustria: Austrian Medicines and Medical Devices AgencyCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Russia: Pharmacological Committee, Ministry of HealthSweden: Medical Products AgencyUnited 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: 291
• 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
• Tiotropium + Olodaterol
Tiotropium 2.5 mcg + olodaterol 5 mcg once daily
• tiotropium + Olodaterol
tiotropium 5 mcg + olodaterol 5 mcg once daily
• Tiotropium
tiotropium
• Olodaterol
Olodaterol 5 mcg once daily

Device:
• Respimat
Respimat inhaler

Locations

Country	Name	City	State
Argentina	1237.14.54402 Boehringer Ingelheim Investigational Site	Buenos Aires
Argentina	1237.14.54401 Boehringer Ingelheim Investigational Site	Mendoza
Austria	1237.14.43402 Boehringer Ingelheim Investigational Site	Grieskirchen
Austria	1237.14.43401 Boehringer Ingelheim Investigational Site	Neumarkt am Wallersee
Canada	1237.14.11402 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1237.14.11401 Boehringer Ingelheim Investigational Site	Ste-Foy	Quebec
Canada	1237.14.11403 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1237.14.11404 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Germany	1237.14.49406 Boehringer Ingelheim Investigational Site	Bamberg
Germany	1237.14.49404 Boehringer Ingelheim Investigational Site	Bochum
Germany	1237.14.49401 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1237.14.49405 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1237.14.49403 Boehringer Ingelheim Investigational Site	Hannover
Germany	1237.14.49402 Boehringer Ingelheim Investigational Site	Kiel
Netherlands	1237.14.31001 Boehringer Ingelheim Investigational Site	Heerlen
Netherlands	1237.14.31005 Boehringer Ingelheim Investigational Site	Hoofddorp
Netherlands	1237.14.31004 Boehringer Ingelheim Investigational Site	Hoorn
Netherlands	1237.14.31006 Medisch Centrum Leeuwarden	Leeuwarden
Netherlands	1237.14.31007 Boehringer Ingelheim Investigational Site	Leiden
Russian Federation	1237.14.70401 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1237.14.70402 Boehringer Ingelheim Investigational Site	St. Petersburg
Sweden	1237.14.46001 Boehringer Ingelheim Investigational Site	Lund
United States	1237.14.01414 Boehringer Ingelheim Investigational Site	Austell	Georgia
United States	1237.14.01417 Boehringer Ingelheim Investigational Site	Baltimore	Maryland
United States	1237.14.01409 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina
United States	1237.14.01412 Boehringer Ingelheim Investigational Site	Dallas	Texas
United States	1237.14.01407 Boehringer Ingelheim Investigational Site	Greenville	South Carolina
United States	1237.14.01404 Boehringer Ingelheim Investigational Site	Phoenix	Arizona
United States	1237.14.01418 Boehringer Ingelheim Investigational Site	Rochester	Minnesota
United States	1237.14.01410 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	1237.14.01403 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina
United States	1237.14.01408 Boehringer Ingelheim Investigational Site	St. Charles	Missouri
United States	1237.14.01401 Boehringer Ingelheim Investigational Site	Union	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Canada,  Germany,  Netherlands,  Russian Federation,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inspiratory Capacity at Rest Before Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Work Capacity	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% 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 (Borg Scale) During Constant Work Rate Cycle Ergometry to Symptom Limitation at 75% Wcap	Slope of the intensity of breathing discomfort (Borg Scale) during CWRCE to symptom limitation at 75% Wcap. The intensity of breathing discomfort was rated using the modified Borg scale with ratings from 0 (nothing at all) to 10 (maximal).; Slope 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	FEV1 (1 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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