Effect of Treatment BI 1744 CL (5 and 10 mcg) Versus Placebo on Exercise Endurance Time During Constant Work Rate Cycle Ergometry II

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

Randomised, Double-blind, Placebo-controlled, 3-way Cross-over Study to Determine the Effect of Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 µg] and 10 µg [2 Actuations of 5 µg]) Delivered by the Respimat® Inhaler on Exercise Endurance Time During Constant Work Rate Cycle Ergometry in Patients With Chronic Obstructive Pulmonary Disease.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01040793
• Other study ID #: 1222.38
• Secondary ID: 2009-014416-35
• Status: Completed
• Phase: Phase 3
• First received: December 29, 2009
• Last updated: July 4, 2014
• Start date: January 2010

Study information

• Verified date: July 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Office for Safety in Health CareBelgium: Federal Agency for Medicinal and Health ProductsCanada: Health CanadaGermany: Federal Institute for Drugs and Medical DevicesRussia: Pharmacological Committee, Ministry of Health
• Study type: Interventional

Clinical Trial Summary

To compare the effects of BI 1744 CL versus placebo on exercise tolerance after 6 weeks of treatment in patients with Chronic Obstructive Pulmonary Disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 157
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 75 Years

Eligibility

Inclusion criteria:

1. Signed informed consent prior to participation.

2. Diagnosis of chronic obstructive pulmonary disease and post-bronchodilator FEV1(Forced Expiratory Volume in 1 sec) <80% of predicted normal and post-bronchodilator FEV1(Forced Expiratory Volume in 1 sec)/FVC of < 70% at Visit 1.

3. Male or female between 40 and 75 years of age.

4. Current or ex-smokers with smoking history of more than 10-pack years.

5. Able to perform technically acceptable pulmonary function tests, multiple exercise tests and able to maintain records.

6. Able to inhale medication in a competent manner from a metered-dose inhaler and Respimat inhaler.

Exclusion criteria:

1. 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.

2. Patients with a history of asthma and/or total blood eosinophil count of 600 cells/mm3.

3. Patients with thyrotoxicosis, paroxysmal tachycardia (>100 beats per minute).

4. Patients with a history of myocardial infarction within 1 year of screening visit, unstable or life-threatening cardiac arrhythmia, hospitalization for heart failure within the past year, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, life-threatening pulmonary obstruction, cystic fibrosis, clinically evident bronchiectasis, significant alcohol or drug abuse or contraindications to exercise.

5. Patients who have undergone thoracotomy with pulmonary resection.

6. Patients being treated with oral beta-adrenergics or oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.

7. Patients who regularly use daytime oxygen for more than one hour per day.

8. 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.

9. Patients who have a limitation of exercise performance as a result of factors other than fatigue or exertional dyspnea.

10. Pregnant or nursing women.

11. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).

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:
• Olodaterol (BI 1744)
Comparison of low and high dose on exercise endurance time in COPD patients
• Olodaterol (BI 1744)
Comparison of low and high dose on exercise endurance time in COPD patients
• Placebo
Comparison of low and high dose and placebo on exercise endurance time in COPD patients
• Olodaterol (BI1744)
Comparison of low and high dose on exercise endurance time in COPD patients
• Olodaterol (BI 1744) placebo
Placebo that represents olodaterol

Locations

Country	Name	City	State
Austria	1222.38.4380 Boehringer Ingelheim Investigational Site	Hallein
Austria	1222.38.4381 Boehringer Ingelheim Investigational Site	Leoben
Belgium	1222.38.32004 Boehringer Ingelheim Investigational Site	Brussel
Belgium	1222.38.32002 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1222.38.32001 Boehringer Ingelheim Investigational Site	Leuven
Belgium	1222.38.32003 Boehringer Ingelheim Investigational Site	Liège
Canada	1222.38.1081 Boehringer Ingelheim Investigational Site	Hamilton	Ontario
Canada	1222.38.1080 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1222.38.1083 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1222.38.1082 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Germany	1222.38.4980 Boehringer Ingelheim Investigational Site	Berlin
Germany	1222.38.4983 Boehringer Ingelheim Investigational Site	Dortmund
Germany	1222.38.4984 Boehringer Ingelheim Investigational Site	Großhansdorf
Germany	1222.38.4981 Boehringer Ingelheim Investigational Site	Kiel
Germany	1222.38.4986 Boehringer Ingelheim Investigational Site	Koblenz
Germany	1222.38.4985 Boehringer Ingelheim Investigational Site	Köln
Russian Federation	1222.38.7080 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1222.38.7081 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1222.38.7082 Boehringer Ingelheim Investigational Site	St. Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  Belgium,  Canada,  Germany,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjusted Mean Endurance Time After 6 Weeks	Primary endpoint was endurance time during constant work rate ergometry to symptom limitation at 75% of maximal work capacity after 6 weeks of treatment. Mixed effects model on log10 transformation data. Adjusted means are back transformed to report as geometric means. Standard errors (SEs) are calculated using the delta method.	6 weeks	No
Secondary	Adjusted Mean Inspiratory Capacity at Isotime After 6 Weeks	Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.	6 weeks	No
Secondary	Adjusted Mean Borg Scale of Breathing Discomfort at Isotime After 6 Weeks	Isotime is defined as the endurance time of the constant work rate exercise test of shortest duration from Baseline visit, and Week 6 of each of the three treatment periods.; Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.	6 weeks	No
Secondary	Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Borg Scale of Breathing Discomfort at Pre-exercise After 6 Weeks	Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.	6 weeks	No
Secondary	Adjusted Mean Borg Scale of Breathing Discomfort at End of Exercise After 6 Weeks	Borg scale rates discomfort with breathing at rest, during exercise and at end-exercise on a scale from 0=Nothing at all to 10=Maximal discomfort.	6 weeks	No
Secondary	Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks	No
Secondary	Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks	Measured using body plethysmography	6 weeks	No
Secondary	Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks	No
Secondary	Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks	No
Secondary	Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks	Measured using body plethysmography	6 weeks	No
Secondary	Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks		6 weeks	No
Secondary	Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks		6 weeks	No
Secondary	Change From Baseline to Day 43 in Blood Pressure	Change from Baseline to Day 43 in Blood Pressure with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.	Baseline and Week 6	No
Secondary	Change From Baseline to Day 43 in Pulse Rate	Change from Baseline to Day 43 in Pulse rate with spirometry. Baseline is defined as mean of pre-treatment values at a given time point.	Baseline and Week 6	No
Secondary	Number of Patients With Notable Changes in Heart Rate	Number of Patients with notable changes in heart rate (HR). Notable HR increase defined as >=25% increase and on-treatment HR > 100 bpm; Notable HR decrease defined as >=25% decrease and on-treatment HR < 50 bpm.	Baseline and Week 6	No
Secondary	Number of Patients With Notable Increase in PR Intervals	Number of Patients with notable increase in PR intervals. Notable PR interval increase defined as >=25% increase and on-treatment PR interval > 200 ms.	Baseline and Week 6	No
Secondary	Number of Patients With Notable Increase in QRS Intervals	Number of Patients with notable increase in QRS intervals. Notable QRS interval increase defined as >=10% increase and on-treatment QRS interval > 110 ms.	Baseline and Week 6	No