An Efficacy and Safety Study to Compare Three Doses of BEA 2180 BR to Tiotropium and Placebo in the Respimat Inhaler.

Pulmonary Disease, Chronic Obstructive Clinical Trial

Official title:

A Multinational, Randomised, Double-blind, Placebo- and Active-controlled, Parallel Group Efficacy and Safety Comparison Over 24 Weeks of Three Doses (50µg, 100µg, 200µg) of BEA 2180 BR to Tiotropium 5µg, Delivered by the Respimat Inhaler and Placebo in Patients With Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00528996
• Other study ID #: 1205.14
• Secondary ID: 2007-007946-42
• Status: Completed
• Phase: Phase 2
• Start date: September 6, 2007
• Est. completion date: May 5, 2009

Study information

• Verified date: July 2021
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to compare the bronchodilator efficacy of three doses (50 µg, 100 µg and 200 µg) of BEA 2180 delivered by the Respimat® once daily to placebo and tiotropium bromide delivered by the Respimat® in patients with COPD. Additional objectives include comparing the effects on dyspnea and health status.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2080
• Est. completion date: May 5, 2009
• Est. primary completion date: May 5, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 100 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 (P95 4381) and must meet the following spirometric criteria:

Patients must have relatively stable, moderate to severe airway obstruction with an FEV1 (post-bronchodilator, 30 minutes post salbutamol/albuterol) <80% of predicted normal and FEV1 less than or equal to 70% of FVC at the PFTs at Visit 1 (screening).

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 electronic PEFR measurements, and must be able to maintain records (Patient Daily 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 (Appendix I)

Exclusion Criteria:

1. Patients with significant diseases other than COPD will be excluded. A significant disease is defined as a disease which in the opinion of the investigator may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient ability to participate in the study.

2. Patients with clinically relevant abnormal baseline haematology, blood chemistry or urinalysis, if the abnormality defines a significant disease as defined in exclusion criterion No. 1.

3. Patients with a recent history (one year or less) of myocardial infarction.

4. Patients with any unstable or life-threatening cardiac arrhythmia.

5. Patients who have been hospitalized for heart failure within the past 3 years.

6. Patients with a malignancy for which the patient has undergone resection, radiation therapy or chemotherapy within the last five years. Patients with treated basal cell carcinoma are allowed.

7. Patients with known symptomatic prostatic hyperplasia or bladder neck obstruction as defined in exclusion criteria No. 1.

8. Patients with known narrow-angle glaucoma.

9. Patients with asthma or a history of asthma.

10. Patients with a history of life-threatening pulmonary obstruction, or a history of cystic fibrosis or clinically evident bronchiectasis.

11. Patients with known active tuberculosis.

12. Patients with a history of and/or active significant alcohol or drug abuse. See exclusion criterion No. 1.

Related Conditions & MeSH terms

• Lung Diseases
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• BEA 2180 BR
Solution
• Tiotropium Bromide
Solution
• Placebo
Solution

Locations

Country	Name	City	State
Canada	1205.14.143 Boehringer Ingelheim Investigational Site	Burlington	Ontario
Canada	1205.14.142 Boehringer Ingelheim Investigational Site	Downsview	Ontario
Canada	1205.14.151 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1205.14.150 Boehringer Ingelheim Investigational Site	Grimsby	Ontario
Canada	1205.14.149 Boehringer Ingelheim Investigational Site	Mississauga	Ontario
Canada	1205.14.146 Boehringer Ingelheim Investigational Site	Quebec
Canada	1205.14.145 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec
Canada	1205.14.148 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador
Canada	1205.14.144 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
Germany	1205.14.381 Boehringer Ingelheim Investigational Site	Aschaffenburg
Germany	1205.14.164 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.167 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.168 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.172 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.175 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.177 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.178 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.377 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.382 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.387 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.388 Boehringer Ingelheim Investigational Site	Berlin
Germany	1205.14.165 Boehringer Ingelheim Investigational Site	Bonn
Germany	1205.14.176 Boehringer Ingelheim Investigational Site	Cottbus
Germany	1205.14.171 Boehringer Ingelheim Investigational Site	Dortmund
Germany	1205.14.379 Boehringer Ingelheim Investigational Site	Geesthacht
Germany	1205.14.174 Boehringer Ingelheim Investigational Site	Gelnhausen
Germany	1205.14.173 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1205.14.375 Boehringer Ingelheim Investigational Site	Hannover
Germany	1205.14.378 Boehringer Ingelheim Investigational Site	Koblenz
Germany	1205.14.170 Boehringer Ingelheim Investigational Site	Lübeck
Germany	1205.14.162 Boehringer Ingelheim Investigational Site	Mainz
Germany	1205.14.384 Boehringer Ingelheim Investigational Site	Marburg
Germany	1205.14.166 Boehringer Ingelheim Investigational Site	Minden
Germany	1205.14.372 Boehringer Ingelheim Investigational Site	Neumünster
Germany	1205.14.386 Boehringer Ingelheim Investigational Site	Neuruppin
Germany	1205.14.385 Boehringer Ingelheim Investigational Site	Oschersleben
Germany	1205.14.169 Boehringer Ingelheim Investigational Site	Rüdersdorf
Germany	1205.14.179 Boehringer Ingelheim Investigational Site	Rüsselsheim
Germany	1205.14.376 Boehringer Ingelheim Investigational Site	Saarbrücken
Germany	1205.14.374 Boehringer Ingelheim Investigational Site	Schwetzingen
Germany	1205.14.371 Boehringer Ingelheim Investigational Site	Witten
Germany	1205.14.373 Boehringer Ingelheim Investigational Site	Witten
Hungary	1205.14.279 Boehringer Ingelheim Investigational Site	Budakeszi
Hungary	1205.14.273 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1205.14.283 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1205.14.287 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1205.14.286 Boehringer Ingelheim Investigational Site	Cegled
Hungary	1205.14.281 Boehringer Ingelheim Investigational Site	Debrecen
Hungary	1205.14.272 Boehringer Ingelheim Investigational Site	Deszk
Hungary	1205.14.289 Boehringer Ingelheim Investigational Site	Deszk
Hungary	1205.14.271 Boehringer Ingelheim Investigational Site	Erd
Hungary	1205.14.276 Boehringer Ingelheim Investigational Site	Gödöllö
Hungary	1205.14.282 Boehringer Ingelheim Investigational Site	Gyula
Hungary	1205.14.277 Boehringer Ingelheim Investigational Site	Komarom
Hungary	1205.14.278 Boehringer Ingelheim Investigational Site	Matrahaza
Hungary	1205.14.280 Boehringer Ingelheim Investigational Site	Mosonmagyarovar
Hungary	1205.14.285 Boehringer Ingelheim Investigational Site	Sopron
Hungary	1205.14.275 Boehringer Ingelheim Investigational Site	Szarvas
Hungary	1205.14.288 Boehringer Ingelheim Investigational Site	Szazhalombatta
Hungary	1205.14.284 Boehringer Ingelheim Investigational Site	Tatabanya
Hungary	1205.14.274 Boehringer Ingelheim Investigational Site	Zalaegerszeg
Korea, Republic of	1205.14.225 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1205.14.228 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1205.14.227 Boehringer Ingelheim Investigational Site	Seongdong-gu
Korea, Republic of	1205.14.221 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1205.14.222 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1205.14.223 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1205.14.224 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1205.14.226 Boehringer Ingelheim Investigational Site	Seoul
Mexico	1205.14.117 Boehringer Ingelheim Investigational Site	Ciudad de Mexico
Mexico	1205.14.108 Boehringer Ingelheim Investigational Site	Cuernavaca, Mor. México
Mexico	1205.14.101 Boehringer Ingelheim Investigational Site	Hermosillo, Sonora
Mexico	1205.14.119 Boehringer Ingelheim Investigational Site	Metepec
Mexico	1205.14.120 Boehringer Ingelheim Investigational Site	Mexico City
Mexico	1205.14.102 Boehringer Ingelheim Investigational Site	Monterrey
Mexico	1205.14.116 Boehringer Ingelheim Investigational Site	Monterrey, Nuevo León
Mexico	1205.14.105 Boehringer Ingelheim Investigational Site	Zapopan, Jal.
Poland	1205.14.251 Boehringer Ingelheim Investigational Site	Chrzanow
Poland	1205.14.253 Boehringer Ingelheim Investigational Site	Gdansk
Poland	1205.14.254 Boehringer Ingelheim Investigational Site	Gdansk
Poland	1205.14.246 Boehringer Ingelheim Investigational Site	Krakow
Poland	1205.14.241 Boehringer Ingelheim Investigational Site	Lodz
Poland	1205.14.242 Boehringer Ingelheim Investigational Site	Lodz
Poland	1205.14.255 Boehringer Ingelheim Investigational Site	Miechow
Poland	1205.14.248 Boehringer Ingelheim Investigational Site	Ruda Slaska
Poland	1205.14.249 Boehringer Ingelheim Investigational Site	Tarnowskie Gory
Poland	1205.14.252 Boehringer Ingelheim Investigational Site	Wilkowice
Poland	1205.14.243 Boehringer Ingelheim Investigational Site	Wroclaw
Poland	1205.14.244 Boehringer Ingelheim Investigational Site	Wroclaw
Poland	1205.14.245 Boehringer Ingelheim Investigational Site	Wroclaw
Poland	1205.14.247 Boehringer Ingelheim Investigational Site	Zabrze
Russian Federation	1205.14.301 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.302 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.303 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.304 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.305 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.306 Boehringer Ingelheim Investigational Site	Moscow
Russian Federation	1205.14.310 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1205.14.311 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1205.14.312 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1205.14.313 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1205.14.314 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1205.14.307 Boehringer Ingelheim Investigational Site	Yaroslavl
Russian Federation	1205.14.308 Boehringer Ingelheim Investigational Site	Yaroslavl
Russian Federation	1205.14.309 Boehringer Ingelheim Investigational Site	Yaroslavl
Spain	1205.14.182 Boehringer Ingelheim Investigational Site	Badajoz
Spain	1205.14.186 Boehringer Ingelheim Investigational Site	Cáceres
Spain	1205.14.183 Boehringer Ingelheim Investigational Site	Madrid
Spain	1205.14.191 Boehringer Ingelheim Investigational Site	Málaga
Spain	1205.14.181 Boehringer Ingelheim Investigational Site	Terrassa (Barcelona)
Spain	1205.14.190 Boehringer Ingelheim Investigational Site	Torrevieja
Spain	1205.14.189 Boehringer Ingelheim Investigational Site	Valencia
Spain	1205.14.187 Boehringer Ingelheim Investigational Site	Vigo
Taiwan	1205.14.207 Boehringer Ingelheim Investigational Site	Changhua
Taiwan	1205.14.208 Boehringer Ingelheim Investigational Site	Chiayi City
Taiwan	1205.14.210 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1205.14.209 Boehringer Ingelheim Investigational Site	Kaohsiung County
Taiwan	1205.14.205 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1205.14.206 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1205.14.202 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1205.14.204 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1205.14.201 Boehringer Ingelheim Investigational Site	Taoyuan County
United States	1205.14.010 Boehringer Ingelheim Investigational Site	Albuquerque	New Mexico
United States	1205.14.036 Boehringer Ingelheim Investigational Site	Ann Arbor	Michigan
United States	1205.14.007 Boehringer Ingelheim Investigational Site	Atlanta	Georgia
United States	1205.14.013 Boehringer Ingelheim Investigational Site	Bay Pines	Florida
United States	1205.14.042 Boehringer Ingelheim Investigational Site	Berkeley	California
United States	1205.14.044 Boehringer Ingelheim Investigational Site	Brick	New Jersey
United States	1205.14.029 Boehringer Ingelheim Investigational Site	Charleston	South Carolina
United States	1205.14.056 Boehringer Ingelheim Investigational Site	Cherry Hill	New Jersey
United States	1205.14.018 Boehringer Ingelheim Investigational Site	Chesterfield	Missouri
United States	1205.14.016 Boehringer Ingelheim Investigational Site	Clearwater	Florida
United States	1205.14.014 Boehringer Ingelheim Investigational Site	Coeur d'Alene	Idaho
United States	1205.14.048 Boehringer Ingelheim Investigational Site	DeLand	Florida
United States	1205.14.041 Boehringer Ingelheim Investigational Site	Denver	Colorado
United States	1205.14.027 Boehringer Ingelheim Investigational Site	Fort Collins	Colorado
United States	1205.14.045 Boehringer Ingelheim Investigational Site	Fort Worth	Texas
United States	1205.14.055 Boehringer Ingelheim Investigational Site	Greer	South Carolina
United States	1205.14.025 Boehringer Ingelheim Investigational Site	Houston	Texas
United States	1205.14.061 Boehringer Ingelheim Investigational Site	Jasper	Alabama
United States	1205.14.005 Boehringer Ingelheim Investigational Site	Johnston	Rhode Island
United States	1205.14.060 Boehringer Ingelheim Investigational Site	Killeen	Texas
United States	1205.14.017 Boehringer Ingelheim Investigational Site	La Jolla	California
United States	1205.14.022 Boehringer Ingelheim Investigational Site	Lakewood	California
United States	1205.14.062 Boehringer Ingelheim Investigational Site	Larchmont	New York
United States	1205.14.019 Boehringer Ingelheim Investigational Site	Livonia	Michigan
United States	1205.14.031 Boehringer Ingelheim Investigational Site	Medford	Oregon
United States	1205.14.028 Boehringer Ingelheim Investigational Site	Mineola	New York
United States	1205.14.054 Boehringer Ingelheim Investigational Site	Mobile	Alabama
United States	1205.14.001 Boehringer Ingelheim Investigational Site	Morgantown	West Virginia
United States	1205.14.030 Boehringer Ingelheim Investigational Site	New Hyde Park	New York
United States	1205.14.057 Boehringer Ingelheim Investigational Site	New Orleans	Louisiana
United States	1205.14.021 Boehringer Ingelheim Investigational Site	New York	New York
United States	1205.14.012 Boehringer Ingelheim Investigational Site	Oklahoma City	Oklahoma
United States	1205.14.035 Boehringer Ingelheim Investigational Site	Olathe	Kansas
United States	1205.14.043 Boehringer Ingelheim Investigational Site	Panama City	Florida
United States	1205.14.003 Boehringer Ingelheim Investigational Site	Philadelphia	Pennsylvania
United States	1205.14.004 Boehringer Ingelheim Investigational Site	Pittsburgh	Pennsylvania
United States	1205.14.033 Boehringer Ingelheim Investigational Site	Reno	Nevada
United States	1205.14.023 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1205.14.024 Boehringer Ingelheim Investigational Site	Richmond	Virginia
United States	1205.14.046 Boehringer Ingelheim Investigational Site	Riverside	California
United States	1205.14.026 Boehringer Ingelheim Investigational Site	Roanoke	Virginia
United States	1205.14.032 Boehringer Ingelheim Investigational Site	Saint Louis	Missouri
United States	1205.14.002 Boehringer Ingelheim Investigational Site	San Antonio	Texas
United States	1205.14.008 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1205.14.047 Boehringer Ingelheim Investigational Site	San Diego	California
United States	1205.14.037 Boehringer Ingelheim Investigational Site	Sepulveda	California
United States	1205.14.052 Boehringer Ingelheim Investigational Site	Shreveport	Louisiana
United States	1205.14.020 Boehringer Ingelheim Investigational Site	Spartanburg	South Carolina
United States	1205.14.009 Boehringer Ingelheim Investigational Site	Spokane	Washington
United States	1205.14.039 Boehringer Ingelheim Investigational Site	Spokane	Washington
United States	1205.14.050 Boehringer Ingelheim Investigational Site	Stamford	Connecticut
United States	1205.14.053 Boehringer Ingelheim Investigational Site	Stockbridge	Georgia
United States	1205.14.058 Boehringer Ingelheim Investigational Site	Summit	New Jersey
United States	1205.14.040 Boehringer Ingelheim Investigational Site	Tampa	Florida
United States	1205.14.059 Boehringer Ingelheim Investigational Site	Toledo	Ohio
United States	1205.14.034 Boehringer Ingelheim Investigational Site	Wheat Ridge	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Hungary,  Korea, Republic of,  Mexico,  Poland,  Russian Federation,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Trough Forced Expiratory Volume in One Second (FEV1) Response After 24 Weeks	Trough Forced expiratory volume in one second (FEV1) response was defined as the change from baseline in trough FEV1. Trough FEV1 was defined as the mean of the two FEV1 measurements recorded at the pre-dose measurements (40 and 15 minutes before the drug administration) at the end of the dosing interval (24 hours post previous drug administration from the Respimat® Inhaler). Baseline FEV1 was pre-treatment FEV1 values measured at Day 1 of treatment period (baseline) prior to administration of the first dose of study medication, which was the mean of the measurements recorded from the pulmonary function tests taken at 40 and 15 minutes prior to drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration at baseline (Day 1 of treatment period) and Week 24.
Secondary	Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks	Trough Forced expiratory volume in one second (FEV1) response was defined as the change from baseline in trough FEV1. Trough FEV1 was defined as the mean of the two FEV1 measurements recorded at the pre-dose measurements (40 and 15 minutes before the drug administration) at the end of the dosing interval (24 hours post previous drug administration from the Respimat® Inhaler). Baseline FEV1 was pre-treatment FEV1 values measured at Day 1 of treatment period (baseline) prior to administration of the first dose of study medication, which was the mean of the measurements recorded from the pulmonary function tests taken at 40 and 15 minutes prior to drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration at baseline (Day 1 of treatment period) and Week 1, 2, 4, 8, 12 and 18.
Secondary	Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks	Trough forced vital capacity (FVC) response was defined as the change from baseline in trough FVC. Trough FVC was defined as the mean of the two FVC measurements recorded at the pre-dose measurements (40 and 15 minutes before drug administration) at the end of the dosing interval (24 hours post previous drug administration from the Respimat® Inhaler), which were obtained through spirometry at the same time points as for forced expiratory volume in one second. Baseline FVC was the mean of the two measurements of FVC taken at 40 and 15 minutes before drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration at baseline (Day 1 of treatment period) and Week 1, 2, 4, 8, 12, 18, and 24.
Secondary	Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 3 Hours (AUC0-3h) Response After 0, 4, 12 and 24 Weeks	Forced expiratory volume in one second (FEV1) area under the curve from 0 to 3 hours (AUC0-3h) response after 0, 4, 12 and 24 weeks are reported. The FEV1 AUC0-3h response is the area under the curve from 0 to 3 hours post drug administration for change from baseline values of FEV1. The area under the curve (AUC) is calculated as the area under the curve from 0 to 3 hours at weeks 0, 4, 12 and 24 using the trapezoidal rule and using planned time, divided by the full duration (3 hours) to report in litres. The mean of the pre-dose values (at 40 minutes and 15 minutes before dosing) are used with a time value of zero for calculating the AUC values starting at zero. The baseline FEV1 is the mean of the two measurements taken at 40 and 15 minutes before drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration and 15 min, 30 min, 60 min, 2 hours, 3 hours after drug administration at Week 0 (Day 1 of treatment period), 4, 12, 24.
Secondary	Forced Vital Capacity (FVC) Area Under the Curve From 0 to 3 Hours (AUC0-3h) Response After 0, 4, 12 and 24 Weeks	Forced vital capacity (FVC) area under the curve from 0 to 3 hours (AUC0-3h) response after 0, 4, 12 and 24 weeks are reported. The FVC AUC0-3h response is the area under the curve from 0 to 3 hours post drug administration for change from baseline values of FVC. The area under the curve (AUC) is calculated as the area under the curve from 0 to 3 hours at weeks 0, 4, 12 and 24 using the trapezoidal rule and using planned time, divided by the full duration (3 hours) to report in litres. The mean of the pre-dose values (at 40 minutes and 15 minutes before dosing) are used with a time value of zero for calculating the AUC values starting at zero. The baseline FVC is the mean of the two measurements taken at 40 and 15 minutes before drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration and 15 min, 30 min, 60 min, 2 hours, 3 hours after drug administration at Week 0 (Day 1 of treatment period), 4, 12, 24.
Secondary	Forced Expiratory Volume in One Second (FEV1) Peak Response After 0, 4, 12, and 24 Weeks	Forced expiratory volume in one second (FEV1) peak response after 0, 4, 12, and 24 weeks were reported. Peak FEV1 response was the maximum change from baseline for the post-dose measurements of FEV1. Baseline FEV1 is the mean of the two measurements taken at 40 and 15 minutes before drug administration.	40 minutes (min) and 15 min before drug administration and 15 min, 30 min, 60 min, 2 hours, 3 hours after drug administration at Week 0 (Day 1 of treatment period), 4, 12, 24.
Secondary	Forced Vital Capacity (FVC) Peak Response After 0, 4, 12, and 24 Weeks	Forced Vital Capacity (FVC) peak response after 0, 4, 12, and 24 weeks were reported. Peak FVC response was the maximum change from baseline for the post-dose measurements of FVC. Baseline FVC is the mean of the two measurements taken at 40 and 15 minutes before drug administration.	40 minutes (min) and 15 min before drug administration and 15 min, 30 min, 60 min, 2 hours, 3 hours after drug administration at Week 0 (Day 1 of treatment period), 4, 12, 24.
Secondary	Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point	Individual Forced expiratory volume in one second (FEV1) values measured at each time points at Week 0, 4, 12, and 24 were reported.	15 minutes (min), 30 min, 1 hour (h), 2 h, 3 h after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24. At 0 min (at drug administration) at Week 4, 12, and 24.
Secondary	Individual Forced Vital Capacity (FVC) Measurements at Each Time Point	Individual Forced Vital Capacity (FVC) values measured at each time point at Week 0, 4, 12, and 24 were reported.	15 minutes (min), 30 min, 1 hour (h), 2 h, 3 h after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24. At 0 min (at drug administration) at Week 4, 12, and 24.
Secondary	Trough Forced Expiratory Volume in One Second (FEV1) Response on Day 3 and 5	Trough Forced expiratory volume in one second (FEV1) response on Day 3 and 5 are reported, for which the FEV1 response is the change from baseline in trough FEV1. Trough FEV1 for respective day (Day 3 or Day 5)was defined as the mean of the two FEV1 measurements recorded at the pre-dose measurements (40 and 15 minutes before the drug administration) at the end of the dosing interval (24 hours post previous drug administration from the Respimat® Inhaler) at that day. Baseline FEV1 was pre-treatment FEV1 values measured at Day 1 of treatment period (baseline) prior to administration of the first dose of study medication, which was the mean of the measurements recorded from the pulmonary function tests taken at 40 and 15 minutes prior to drug administration at Day 1 of treatment period.	40 minutes (min) and 15 min before drug administration at Day 1 (baseline) and Day 3 and 5 of treatment period.
Secondary	Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration	Forced expiratory volume in one second (FEV1) values at 3 minutes and 10 minutes following drug administration at Week 0, 4, 12, and 24 are reported.	3 minutes (min) and 10 after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24.
Secondary	Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration	Forced Vital Capacity (FVC) values at 3 minutes and 10 minutes following drug administration at Week 0, 4, 12, and 24 are reported.	3 minutes (min) and 10 min after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24.
Secondary	Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR)	The patient recorded twice daily peak flow measurements with an electronic peak flow meter throughout the entire evaluation period. Morning measurements were performed immediately upon arising after the patient had cleared out mucus, prior to administration of trial and/or rescue medication. The evening measurements were performed at bedtime. The weekly mean morning peak expiratory flow rate (PEFR) is reported.	Assessed before drug administration per day during 24 weeks with weekly mean values reporting.
Secondary	Weekly Mean Evening Peak Expiratory Flow Rate (PEFR)	The patient recorded twice daily peak flow measurements with an electronic peak flow meter throughout the entire evaluation period. Morning measurements were performed immediately upon arising after the patient had cleared out mucus, prior to administration of trial and/or rescue medication. The evening measurements were performed at bedtime. The weekly mean of evening peak expiratory flow rate (PEFR) is reported.	Assessed at bed time per day during 24 weeks with weekly mean values reporting.
Secondary	Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol])	The patient recorded the number of occasions salbutamol (albuterol) Metered Dose Inhaler (MDI) was used each day and night during the entire evaluation period. The weekly mean number of occasions of rescue therapy used per day (PRN salbutamol [albuterol]) is reported.	Assessed once per day during 24 weeks with weekly mean values reporting.
Secondary	Physician's Global Evaluation	Physicians make a global evaluation reflecting the physician's global opinion of the overall clinical condition of the patient as "poor" (score 1 or 2), "fair" (score 3 or 4), "good" (score 5 or 6), or "excellent" (score 7 or 8). These assessments are made prior to pulmonary function testing and are summarized on pulmonary function test days. This evaluation was based on the need for concomitant medication, number and severity of exacerbations since the last visit, severity of cough, ability to exercise, amount of wheezing, and other relevant clinical observations. The score ranges from 1 to 8 with higher score indicating better overall clinical condition.	At Week 0, 4, 12, and 24.
Secondary	Transition Dyspnea Index - Functional Impairment Domain Score	The transitional dyspnea index (TDI) evaluates the patient's condition related to breathlessness. The TDI includes three domains: functional impairment, magnitude of task, and magnitude of effort. The TDI domain score of functional impairment is reported, which domain score ranges from -3 (major deterioration in the ability of working and doing activities due to shortness of breath; the worst score) to 3 (major improvement in the ability of working and doing activities; mild restriction on full activities due to the improvement of shortness of breath; the best score).	At Week 0 (baseline), 4, 12 and 24.
Secondary	Transition Dyspnea Index - Magnitude of Task Domain Score	The transitional dyspnea index (TDI) evaluates the patient's condition related to breathlessness. The TDI includes three domains: functional impairment, magnitude of task, and magnitude of effort. The TDI domain score of magnitude of task is reported, which domain score ranges from -3 (major deterioration from baseline status; the worst score) to 3 (major improvement from baseline status; the best score).	At week 0 (baseline), 4, 12 and 24
Secondary	Transition Dyspnea Index - Magnitude of Effort Domain Score	The transitional dyspnea index (TDI) evaluates the patient's condition related to breathlessness. The TDI includes three domains: functional impairment, magnitude of task, and magnitude of effort. The TDI domain score of magnitude of effort is reported, which sub-score ranges from -3 (severe decrease in effort from baseline to avoid shortness of breath. Activities now take 50-100% longer to complete than required at baseline; the worst score) to 3 (Able to do things with much greater effort than previously with few pauses. Activities may be performed 50- 100% more rapidly than at baseline; the best score).	At Week 0 (baseline), 4, 12 and 24
Secondary	St. George's Respiratory Questionnaire (SGRQ) Total Score	The St. George's Respiratory Questionnaire (SGRQ) is a well-established, self-completed tool measuring health-related quality of life in patients with diseases of airways obstruction on three aspects of symptoms, activity, and impacts. The total SGRQ score is reported, which ranges from 0 (the best score) to 100 (the worst score) with smaller score value indicating less limitations due to breathlessness and better quality of life.	At Week 0, 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) 8 Domain Scores at Baseline	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function (10 questions), role physical (4 questions), Bodily pain (2 questions), General physical health (5 questions), Vitality (4 questions), Social functioning (2 questions), role emotional (3 questions), and General mental health (5 questions). Each domain score is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the score value, the better the health condition.	At baseline (Week 0, Day 1 of treatment period).
Secondary	36-item-health Survey (SF-36) - Physical Function Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of physical function (based on 10 questions) is reported, which is the weighted sum of the questions in corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the better the physical function.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - Role Physical Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of role limitations due to physical health problems (based on 4 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the less limitations in roles due to physical health problems.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - Bodily Pain Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of bodily pain (based on 2 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the less severer the bodily pain.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - General Physical Health Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of general physical health (based on 5 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the better the physical health in general.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - Vitality Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of vitality (based on 4 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the more vitality and less fatigue one has.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - Social Functioning Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of Social functioning (based on 2 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the better the social functioning.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - Role Emotional Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of role emotional (based on 4 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the less limitation in roles due to emotional problems.	At Week 4, 12, and 24.
Secondary	36-item-health Survey (SF-36) - General Mental Health Domain Score	The 36-item-health Survey (SF-36) is a multi-purpose, short-form health survey with 36 questions evaluating patient's physical and mental health. Among the 36 questions, 1 is on the health comparing to 1 year ago and the remaining 35 questions are divided into 8 domains: Physical function, role limitations physical, Bodily pain, General physical health, Vitality, Social functioning, role limitations emotional, and General mental health.; The domain score of general mental health (based on 5 questions) is reported, which is the weighted sum of the questions in the corresponding domain with the domain score ranging from 0 to 100. The higher the domain score, the better the mental health in general.	At Week 4, 12, and 24.
Secondary	Number of Patients With at Least One Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Number of patients with at least one Chronic Obstructive Pulmonary Disease (COPD) exacerbation is reported. Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation is reported. A Chronic Obstructive Pulmonary Disease (COPD) exacerbation is defined as "a complex of lower respiratory events / symptoms (increase or new onset) related to the underlying COPD, with a duration of three days or more, requiring a change in treatment", where a "complex of lower respiratory events / symptoms" means at least two of the following: Shortness of breath, Sputum production (volume), Occurrence of purulent sputum, Cough, Wheezing, Chest tightness.	From first does until 30 days after the end of treatment, up to 205 days.
Secondary	Incidence Rate of Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	Incidence rate of Chronic Obstructive Pulmonary Disease (COPD) exacerbation is reported. A Chronic Obstructive Pulmonary Disease (COPD) exacerbation is defined as "a complex of lower respiratory events / symptoms (increase or new onset) related to the underlying COPD, with a duration of three days or more, requiring a change in treatment", where a "complex of lower respiratory events / symptoms" means at least two of the following: Shortness of breath, Sputum production (volume), Occurrence of purulent sputum, Cough, Wheezing, Chest tightness.	From first does until 30 days after the end of treatment, up to 205 days.

External Links

•   Related Info