Efficacy and Safety of 4 Weeks Treatment With Inhaled BI 1744 CL in Patients With COPD.

Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy and Safety of 4 Weeks of Treatment of Orally Inhaled BI 1744 CL (3 - 4 Doses) Delivered by the Respimat® Inhaler in Patients With COPD

The primary objective of this study is to determine the optimum dose(s) of BI 1744 CL inhalation solution delivered by the Respimat® inhaler for four weeks in patients with chronic obstructive pulmonary disease (COPD). The selection of the optimum dose(s) will be based on bronchodilator efficacy (how well it helps your breathing), safety evaluations and pharmacokinetic evaluations (the amount of the medication found in your blood).

Study Overview

• Status: Completed
• Conditions: Pulmonary Disease, Chronic Obstructive; Asthma
• Intervention / Treatment: Drug: BI 1744CL

• Study Type: Interventional
• Enrollment (Actual): 409
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • 1222.5.039 St. Boniface General Hospital & Health Science Centre
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • 1222.5.032 Division of Respirology
  • Ontario
    • Courtice, Ontario, Canada
      • 1222.5.038 Courtice Health Centre
    • Kingston, Ontario, Canada
      • 1222.5.037 Kingston General Hospital
    • Mississauga, Ontario, Canada
      • 1222.5.031 Alpha Medical Research Inc.
    • Toronto, Ontario, Canada
      • 1222.5.034 Pulmonary Care Clinic and Research Centre
    • Toronto, Ontario, Canada
      • 1222.5.040 Respiratory Research Lab
  • Quebec
    • Sherbrooke, Quebec, Canada
      • 1222.5.033 Centre de Recherche Clinique -CHUS
    • Ste-Foy, Quebec, Canada
      • 1222.5.035 Hopital Laval
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada
      • 1222.5.036 Department of Respiratory Medicine
• Germany
  • Berlin, Germany
    • 1222.5.046 Boehringer Ingelheim Investigational Site
  • Berlin, Germany
    • 1222.5.049 Boehringer Ingelheim Investigational Site
  • Gauting, Germany
    • 1222.5.052 Boehringer Ingelheim Investigational Site
  • Großhansdorf, Germany
    • 1222.5.051 Boehringer Ingelheim Investigational Site
  • Rüdersdorf, Germany
    • 1222.5.047 Boehringer Ingelheim Investigational Site
  • Wiesbaden, Germany
    • 1222.5.048 Boehringer Ingelheim Investigational Site
• Netherlands
  • Almelo, Netherlands
    • 1222.5.058 Boehringer Ingelheim Investigational Site
  • Breda, Netherlands
    • 1222.5.056 Boehringer Ingelheim Investigational Site
  • Eindhoven, Netherlands
    • 1222.5.059 Boehringer Ingelheim Investigational Site
  • Heerlen, Netherlands
    • 1222.5.057 Boehringer Ingelheim Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States
      • 1222.5.03 Boehringer Ingelheim Investigational Site
  • California
    • Lakewood, California, United States
      • 1222.5.07 Boehringer Ingelheim Investigational Site
  • Colorado
    • Denver, Colorado, United States
      • 1222.5.14 Boehringer Ingelheim Investigational Site
    • Wheat Ridge, Colorado, United States
      • 1222.5.17 Boehringer Ingelheim Investigational Site
    • WheatRidge, Colorado, United States
      • 1222.5.13 Boehringer Ingelheim Investigational Site
  • Connecticut
    • Stamford, Connecticut, United States
      • 1222.5.18 Boehringer Ingelheim Investigational Site
  • Florida
    • Panama City, Florida, United States
      • 1222.5.15 Boehringer Ingelheim Investigational Site
  • Idaho
    • Coeur D'Alene, Idaho, United States
      • 1222.5.04 Boehringer Ingelheim Investigational Site
  • Louisiana
    • Shreveport, Louisiana, United States
      • 1222.5.22 Boehringer Ingelheim Investigational Site
  • Nevada
    • Reno, Nevada, United States
      • 1222.5.11 Boehringer Ingelheim Investigational Site
  • New York
    • New York, New York, United States
      • 1222.5.24 Boehringer Ingelheim Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States
      • 1222.5.12 Boehringer Ingelheim Investigational Site
  • Oregon
    • Medford, Oregon, United States
      • 1222.5.10 Boehringer Ingelheim Investigational Site
  • Pennsylvania
    • Hershey, Pennsylvania, United States
      • 1222.5.05 Boehringer Ingelheim Investigational Site
    • Philadelphia, Pennsylvania, United States
      • 1222.5.02 Boehringer Ingelheim Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States
      • 1222.5.08 Boehringer Ingelheim Investigational Site
    • Charleston, South Carolina, United States
      • 1222.5.19 Boehringer Ingelheim Investigational Site
    • Spartanburg, South Carolina, United States
      • 1222.5.06 Boehringer Ingelheim Investigational Site
  • Texas
    • Kileen, Texas, United States
      • 1222.5.21 Boehringer Ingelheim Investigational Site
    • San Antonio, Texas, United States
      • 1222.5.01 Boehringer Ingelheim Investigational Site
  • Virginia
    • Richmond, Virginia, United States
      • 1222.5.23 Boehringer Ingelheim Investigational Site
  • Washington
    • Tacoma, Washington, United States
      • 1222.5.20 Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

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

Description

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, moderate to severe airway obstruction with a post-bronchodilator FEV1  30% of predicted normal and < 80% of predicted normal and a post-bronchodilator FEV1 / FVC < 70% at Visit 1

3. Male or female patients, 40 years of age or older
4. Patients must be current or ex-smokers with a smoking history of more than 10 pack years. Patients who have never smoked cigarettes must be excluded
5. Patients must be able to perform technically acceptable pulmonary function tests and PEFR measurements, and must be able to maintain records (Patient Daily e-Diary) during the study period as required in the protocol
6. Patients must be able to inhale medication in a competent manner from the Respimat® inhaler and from a metered dose inhaler (MDI).

Exclusion Criteria:

Selection of relevant exclusion criteria:

1. Patients with a history of asthma or a total blood eosinophil count 600/mm3.

2. Patients with any of the following conditions:

   • a diagnosis of thyrotoxicosis
   • a diagnosis of paroxysmal tachycardia (>100 beats per minute)
   • a marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval > 450 ms).
   • a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart failure, hypokalemia, family history of Long QT Syndrome)

3. Patients with any of the following conditions:

   • a history of myocardial infarction within 1 year of screening visit (Visit 1)
   • a diagnosis of clinically relevant cardiac arrhythmia
   • known active tuberculosis
   • a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years (patients with treated basal cell carcinoma are allowed)
   • a history of life-threatening pulmonary obstruction
   • a history of cystic fibrosis
   • clinically evident bronchiectasis
   • a history of significant alcohol or drug abuse
4. Patients who have undergone thoracotomy with pulmonary resection
5. 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
6. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the Screening Visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program
7. Patients who have taken an investigational drug within one month or six half lives (whichever is greater) prior to Screening Visit (Visit 1)
8. Pregnant or nursing women
9. Women of childbearing potential not using a highly effective method of birth control
10. Patients who have previously been randomized in this study or are currently participating in another study
11. Patients who are unable to comply with medication restrictions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough FEV1 Response After 4 Weeks	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Relevant Abnormalities for Vital Signs, ECG and Physical Examination	Clinical relevant abnormalities for vital signs, ECG and physical examination. Any new or clinically relevant worsening of baseline conditions was reported as adverse events.	4 weeks
Trough FEV1 Response After 1 Week	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 1 week
Trough FEV1 Response After 2 Weeks	Trough FEV1 is defined as the mean of the two FEV1 values (performed at -1 hour and -10 minutes prior to test-drug inhalation) at the end of the dosing interval, 24 hours post-drug administration. Trough FEV1 response is defined as the change from baseline in trough FEV1. Baseline FEV1 is the mean of the two pre-treatment FEV1 values measured at Visit 2 (- 1 hour and - 10 minutes) prior to administration of the first dose of study medication.	Baseline and 2 weeks
Trough FVC Response After 1 Week	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 1 week
Trough FVC Response After 2 Weeks	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 2 weeks
Trough FVC Response After 4 Weeks	Trough FVC was defined as the mean of the two values obtained at 1 hour and 10 minutes prior to the pulmonary function test maneuver. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	Baseline and 4 weeks
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
Peak FEV1 (0-3h) Response After 4 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
Forced Vital Capacity (FVC) Area Under Curve 0-6 h (AUC 0-6h) Response at Week 4	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FVC AUC 0-6h was calculated from 0-6 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h, 4h, 5h, 6h relative to dose at Week 4
Peak FVC (0-3h) Response After 4 Weeks	Peak (0-3h) will be the maximum post-dose value during the first 3 hours. Response is defined as change from the baseline value. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment.	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 4 weeks
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours postdose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at day 1
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 1
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-3 h (AUC 0-3h) Response at Week 2	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and 30 min, 1h, 2h, 3h relative to dose at Week 2
Peak FEV1 (0-3h) Response At Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment.Means are adjusted using a mixed effects model with baseline,treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose at day 1
Peak FEV1 (0-3h) Response After 1 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 1 week
Peak FEV1 (0-3h) Response After 2 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with baseline, treatment and centre (centre random, all other effects fixed).	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response at Day 1	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	baseline and day1
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 1 Week	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 1 week
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 2 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 2 weeks
Forced Expiratory Volume in 1 Second (FEV1) (Unsupervised) Area Under Curve 6-12 h (AUC 6-12h) Response After 4 Weeks	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a model with treatment (trt), baseline as fixed effects and centre as random effect. FEV1 AUC 6-12h was calculated from 6-12 hours post-dose using the trapezoidal rule, divided by the observation time (6h) to report in litres.	Baseline and 4 weeks
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) After 4 Weeks	Baseline PEFR was defined as the mean of the morning PEFR measurements obtained during the week just prior to first dose of randomized treatment.	4 weeks
Weekly Mean Evening PEFR After 4 Weeks	Baseline PEFR was defined as the mean of the evening PEFR measurements obtained during the week just prior to first dose of randomized treatment.	4 weeks
Weekly Mean Number of Occasions of Rescue Therapy After 4 Weeks	Weekly mean number of occasions of rescue therapy used per day (PRN salbutamol (albuterol))	4 weeks
Area Under Curve From 0 to 3 Hours (AUC0-3)	AUC0-3 represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3.	Baseline and 4 weeks
Maximum Concentration (Cmax)	Cmax represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma.	Baseline and 4 weeks
Time From Dosing to the Maximum Concentration (Tmax)	tmax represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma.	Baseline and 4 weeks
Area Under Curve From 0 to 3 Hours at Steady State (AUC0-3,ss)	AUC0-3,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=3 at steady state.	Baseline and 4 weeks
Area Under Curve From 0 to 6 Hours at Steady State (AUC0-6,ss)	AUC0-6,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=6 at steady state.	Baseline and 4 weeks
Area Under Curve From 0 to 24 Hours at Steady State (AUC0-24,ss)	AUC0-24,ss represents the area under the concentration curve of olodaterol and olodaterol glucuronide in plasma from 0 to time t=24 at steady state.	Baseline and 4 weeks
Maximum Concentration at Steady State (Cmax,ss)	Cmax,ss represents the maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.	Baseline and 4 weeks
Time From Dosing to the Maximum Concentration at Steady State (Tmax,ss)	tmax,ss represents the time from dosing to maximum concentration of olodaterol and olodaterol glucuronide in plasma at steady state.	Baseline and 4 weeks
Laboratory Testing: Average Change From Baseline of Potassium	Laboratory testing: Average change from baseline of potassium measured on test-days. Pre-dose value on test day 1 is the baseline value.	Baseline and day 29

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Maleki-Yazdi MR, Beck E, Hamilton AL, Korducki L, Koker P, Fogarty C. A randomised, placebo-controlled, Phase II, dose-ranging trial of once-daily treatment with olodaterol, a novel long-acting beta2-agonist, for 4 weeks in patients with chronic obstructive pulmonary disease. Respir Med. 2015 May;109(5):596-605. doi: 10.1016/j.rmed.2015.02.012. Epub 2015 Mar 3.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2007
• Primary Completion (Actual): January 1, 2008

Study Registration Dates

• First Submitted: March 26, 2007
• First Submitted That Met QC Criteria: March 26, 2007
• First Posted (Estimate): March 27, 2007

Study Record Updates

• Last Update Posted (Estimate): June 27, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; 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: 1222.5