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

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.

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive
• Intervention / Treatment: Drug: Olodaterol (BI 1744); Drug: Olodaterol (BI1744); Drug: Olodaterol (BI 1744) placebo; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olodaterol (BI 1744) High; High dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI 1744); Comparison of low and high dose on exercise endurance time in COPD patients
Experimental: Olodaterol (BI 1744) Low; Low dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI 1744); Comparison of low and high dose on exercise endurance time in COPD patients; Drug: Olodaterol (BI1744); Comparison of low and high dose on exercise endurance time in COPD patients; Drug: Olodaterol (BI 1744) placebo; Placebo that represents olodaterol
Placebo Comparator: Placebo; Olodaterol (BI 1744) placebo inhaled orally from the Respimat inhaler	Drug: Placebo; Comparison of low and high dose and placebo on exercise endurance time in COPD patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Adjusted Mean Inspiratory Capacity at Pre-exercise After 6 Weeks		6 weeks
Adjusted Mean Inspiratory Capacity at End of Exercise After 6 Weeks		6 weeks
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
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
Adjusted Mean Functional Residual Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks
Adjusted Mean Functional Residual Capacity 1 Hour Post-dose After 6 Weeks	Measured using body plethysmography	6 weeks
Adjusted Mean Inspiratory Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks
Adjusted Mean Inspiratory Capacity 1 Hour Post-dose After 6 Weeks		6 weeks
Adjusted Mean Total Lung Capacity 30 Minutes Pre-dose After 6 Weeks	Measured using body plethysmography	6 weeks
Adjusted Mean Total Lung Capacity 1 Hour Post-dose After 6 Weeks	Measured using body plethysmography	6 weeks
Adjusted Mean Forced Expiratory Volume in 1 Second, 30 Minutes Pre-dose After 6 Weeks		6 weeks
Adjusted Mean Forced Expiratory Volume in 1 Second, 1 Hour Post-dose After 6 Weeks		6 weeks
Adjusted Mean Forced Vital Capacity, 30 Minutes Pre-dose After 6 Weeks		6 weeks
Adjusted Mean Forced Vital Capacity, 1 Hour Post-dose After 6 Weeks		6 weeks
Adjusted Mean Peak Expiratory Flow Rate, 30 Minutes Pre-dose After 6 Weeks		6 weeks
Adjusted Mean Peak Expiratory Flow Rate, 1 Hour Post-dose After 6 Weeks		6 weeks
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Maltais F, Kirsten AM, Hamilton A, De Sousa D, Voss F, Decramer M. Evaluation of the effects of olodaterol on exercise endurance in patients with chronic obstructive pulmonary disease: results from two 6-week crossover studies. Respir Res. 2016 Jul 6;17(1):77. doi: 10.1186/s12931-016-0389-5.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: December 29, 2009
• First Submitted That Met QC Criteria: December 29, 2009
• First Posted (Estimate): December 30, 2009

Study Record Updates

• Last Update Posted (Estimate): July 8, 2014
• Last Update Submitted That Met QC Criteria: July 4, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Olodaterol
• Other Study ID Numbers: 1222.38; 2009-014416-35 (EudraCT Number: EudraCT)