Trial Outcomes & Findings for An Efficacy and Safety Study to Compare Three Doses of BEA 2180 BR to Tiotropium and Placebo in the Respimat Inhaler. (NCT NCT00528996)

Last Updated: 2021-08-24

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

2080 participants

Primary outcome timeframe

40 minutes (min) and 15 min before drug administration at baseline (Day 1 of treatment period) and Week 24.

Results posted on

2021-08-24

Participant Flow

A multinational, randomized, double-blind, placebo-and active-controlled, parallel group efficacy and safety comparison of BEA 2180 to tiotropium and placebo delivered by the Respimat® inhaler in patients with chronic obstructive pulmonary disease (COPD).

All subjects were screened for eligibility to participate in trial. Subjects visited specialist site to ensure that they met all implemented inclusion criteria. Subjects meeting the exclusion criteria were excluded.

Participant milestones

Participant milestones
Measure	Placebo Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Overall Study STARTED	429	419	415	390	427
Overall Study COMPLETED	365	395	372	340	390
Overall Study NOT COMPLETED	64	24	43	50	37

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Overall Study Other reasons than listing	6	7	14	11	5
Overall Study Refused continue medication	16	0	3	3	6
Overall Study Lost to Follow-up	2	0	4	1	3
Overall Study Protocol Violation	1	2	3	3	2
Overall Study Lack of Efficacy	7	2	1	3	3
Overall Study Adverse Event	32	13	18	29	18

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=429 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=419 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=415 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=390 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=427 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.	Total n=2080 Participants Total of all reporting groups
Age, Continuous	64.41 Year STANDARD_DEVIATION 8.57 • n=5 Participants	63.98 Year STANDARD_DEVIATION 8.66 • n=7 Participants	64.60 Year STANDARD_DEVIATION 9.11 • n=5 Participants	63.89 Year STANDARD_DEVIATION 8.88 • n=4 Participants	63.91 Year STANDARD_DEVIATION 8.74 • n=21 Participants	64.16 Year STANDARD_DEVIATION 8.79 • n=8 Participants
Sex: Female, Male Female	155 Participants n=5 Participants	152 Participants n=7 Participants	146 Participants n=5 Participants	140 Participants n=4 Participants	146 Participants n=21 Participants	739 Participants n=8 Participants
Sex: Female, Male Male	274 Participants n=5 Participants	267 Participants n=7 Participants	269 Participants n=5 Participants	250 Participants n=4 Participants	281 Participants n=21 Participants	1341 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	4 Participants n=4 Participants	0 Participants n=21 Participants	14 Participants n=8 Participants
Race (NIH/OMB) Asian	35 Participants n=5 Participants	34 Participants n=7 Participants	34 Participants n=5 Participants	31 Participants n=4 Participants	34 Participants n=21 Participants	168 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	13 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	11 Participants n=21 Participants	58 Participants n=8 Participants
Race (NIH/OMB) White	384 Participants n=5 Participants	371 Participants n=7 Participants	363 Participants n=5 Participants	340 Participants n=4 Participants	382 Participants n=21 Participants	1840 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants
Forced expiratory volume in one second (FEV1)	1.18 liter STANDARD_DEVIATION 0.46 • n=5 Participants	1.18 liter STANDARD_DEVIATION 0.46 • n=7 Participants	1.18 liter STANDARD_DEVIATION 0.48 • n=5 Participants	1.19 liter STANDARD_DEVIATION 0.49 • n=4 Participants	1.20 liter STANDARD_DEVIATION 0.47 • n=21 Participants	1.18 liter STANDARD_DEVIATION 0.47 • n=8 Participants

PRIMARY outcome

Timeframe: 40 minutes (min) and 15 min before drug administration at baseline (Day 1 of treatment period) and Week 24.

Population: The full analysis set (FAS) was defined as all patients in treated set with at least baseline Forced expiratory volume in one second (FEV1) data and at least one acceptable post-treatment trough FEV1 measurement.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Trough Forced Expiratory Volume in One Second (FEV1) Response After 24 Weeks	-0.034 litre Standard Error 0.010	0.044 litre Standard Error 0.010	0.066 litre Standard Error 0.011	0.087 litre Standard Error 0.011	0.092 litre Standard Error 0.010

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 1	-0.014 litre Standard Error 0.008	0.070 litre Standard Error 0.008	0.090 litre Standard Error 0.008	0.106 litre Standard Error 0.009	0.097 litre Standard Error 0.008
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 2	-0.013 litre Standard Error 0.009	0.080 litre Standard Error 0.009	0.094 litre Standard Error 0.009	0.110 litre Standard Error 0.009	0.105 litre Standard Error 0.008
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 4	-0.020 litre Standard Error 0.009	0.066 litre Standard Error 0.009	0.090 litre Standard Error 0.009	0.100 litre Standard Error 0.009	0.099 litre Standard Error 0.009
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 8	-0.006 litre Standard Error 0.010	0.078 litre Standard Error 0.010	0.086 litre Standard Error 0.010	0.101 litre Standard Error 0.010	0.104 litre Standard Error 0.010
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 12	-0.010 litre Standard Error 0.010	0.066 litre Standard Error 0.010	0.083 litre Standard Error 0.010	0.107 litre Standard Error 0.010	0.109 litre Standard Error 0.010
Trough Forced Expiratory Volume in One Second (FEV1) Response After 1, 2, 4, 8, 12, and 18 Weeks Week 18	-0.023 litre Standard Error 0.010	0.063 litre Standard Error 0.010	0.072 litre Standard Error 0.010	0.096 litre Standard Error 0.010	0.096 litre Standard Error 0.010

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 1	-0.002 litre Standard Error 0.015	0.146 litre Standard Error 0.015	0.172 litre Standard Error 0.016	0.186 litre Standard Error 0.016	0.174 litre Standard Error 0.015
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 2	-0.002 litre Standard Error 0.016	0.166 litre Standard Error 0.016	0.177 litre Standard Error 0.016	0.186 litre Standard Error 0.017	0.188 litre Standard Error 0.016
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 4	-0.022 litre Standard Error 0.016	0.132 litre Standard Error 0.016	0.157 litre Standard Error 0.016	0.156 litre Standard Error 0.017	0.169 litre Standard Error 0.016
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 8	0.006 litre Standard Error 0.018	0.148 litre Standard Error 0.018	0.166 litre Standard Error 0.018	0.173 litre Standard Error 0.018	0.177 litre Standard Error 0.018
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 12	0.001 litre Standard Error 0.018	0.121 litre Standard Error 0.018	0.155 litre Standard Error 0.018	0.171 litre Standard Error 0.018	0.178 litre Standard Error 0.018
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 18	-0.023 litre Standard Error 0.018	0.117 litre Standard Error 0.018	0.131 litre Standard Error 0.018	0.153 litre Standard Error 0.019	0.146 litre Standard Error 0.018
Trough Forced Vital Capacity (FVC) Response After 1, 2, 4, 8, 12, 18, and 24 Weeks Week 24	-0.044 litre Standard Error 0.019	0.081 litre Standard Error 0.019	0.104 litre Standard Error 0.019	0.132 litre Standard Error 0.020	0.146 litre Standard Error 0.019

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 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 Week 0	0.029 litre Standard Error 0.007	0.172 litre Standard Error 0.007	0.186 litre Standard Error 0.007	0.177 litre Standard Error 0.007	0.165 litre Standard Error 0.007
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 Week 4	0.021 litre Standard Error 0.010	0.166 litre Standard Error 0.010	0.175 litre Standard Error 0.010	0.165 litre Standard Error 0.011	0.203 litre Standard Error 0.010
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 Week 12	0.019 litre Standard Error 0.011	0.164 litre Standard Error 0.011	0.166 litre Standard Error 0.011	0.166 litre Standard Error 0.011	0.203 litre Standard Error 0.011
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 Week 24	-0.007 litre Standard Error 0.011	0.140 litre Standard Error 0.011	0.150 litre Standard Error 0.011	0.146 litre Standard Error 0.012	0.177 litre Standard Error 0.011

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 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 Week 0	0.067 litre Standard Error 0.015	0.321 litre Standard Error 0.015	0.336 litre Standard Error 0.015	0.302 litre Standard Error 0.015	0.312 litre Standard Error 0.015
Forced Vital Capacity (FVC) Area Under the Curve From 0 to 3 Hours (AUC0-3h) Response After 0, 4, 12 and 24 Weeks Week 4	0.050 litre Standard Error 0.019	0.292 litre Standard Error 0.019	0.298 litre Standard Error 0.020	0.247 litre Standard Error 0.020	0.340 litre Standard Error 0.019
Forced Vital Capacity (FVC) Area Under the Curve From 0 to 3 Hours (AUC0-3h) Response After 0, 4, 12 and 24 Weeks Week 12	0.053 litre Standard Error 0.020	0.276 litre Standard Error 0.020	0.278 litre Standard Error 0.021	0.251 litre Standard Error 0.021	0.326 litre Standard Error 0.020
Forced Vital Capacity (FVC) Area Under the Curve From 0 to 3 Hours (AUC0-3h) Response After 0, 4, 12 and 24 Weeks Week 24	-0.002 litre Standard Error 0.021	0.233 litre Standard Error 0.021	0.218 litre Standard Error 0.022	0.210 litre Standard Error 0.022	0.274 litre Standard Error 0.021

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Forced Expiratory Volume in One Second (FEV1) Peak Response After 0, 4, 12, and 24 Weeks Week 0	0.103 litre Standard Error 0.008	0.246 litre Standard Error 0.008	0.260 litre Standard Error 0.08	0.266 litre Standard Error 0.009	0.246 litre Standard Error 0.008
Forced Expiratory Volume in One Second (FEV1) Peak Response After 0, 4, 12, and 24 Weeks Week 4	0.090 litre Standard Error 0.011	0.237 litre Standard Error 0.011	0.250 litre Standard Error 0.011	0.243 litre Standard Error 0.011	0.274 litre Standard Error 0.011
Forced Expiratory Volume in One Second (FEV1) Peak Response After 0, 4, 12, and 24 Weeks Week 12	0.078 litre Standard Error 0.011	0.236 litre Standard Error 0.011	0.236 litre Standard Error 0.012	0.241 litre Standard Error 0.012	0.273 litre Standard Error 0.011
Forced Expiratory Volume in One Second (FEV1) Peak Response After 0, 4, 12, and 24 Weeks Week 24	0.051 litre Standard Error 0.012	0.207 litre Standard Error 0.012	0.216 litre Standard Error 0.012	0.216 litre Standard Error 0.012	0.242 litre Standard Error 0.012

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Forced Vital Capacity (FVC) Peak Response After 0, 4, 12, and 24 Weeks Week 0	0.216 litre Standard Error 0.018	0.474 litre Standard Error 0.018	0.478 litre Standard Error 0.018	0.463 litre Standard Error 0.019	0.463 litre Standard Error 0.018
Forced Vital Capacity (FVC) Peak Response After 0, 4, 12, and 24 Weeks Week 4	0.186 litre Standard Error 0.021	0.434 litre Standard Error 0.021	0.449 litre Standard Error 0.021	0.386 litre Standard Error 0.022	0.479 litre Standard Error 0.021
Forced Vital Capacity (FVC) Peak Response After 0, 4, 12, and 24 Weeks Week 12	0.177 litre Standard Error 0.022	0.417 litre Standard Error 0.022	0.412 litre Standard Error 0.023	0.384 litre Standard Error 0.023	0.463 litre Standard Error 0.022
Forced Vital Capacity (FVC) Peak Response After 0, 4, 12, and 24 Weeks Week 24	0.122 litre Standard Error 0.023	0.369 litre Standard Error 0.023	0.345 litre Standard Error 0.023	0.335 litre Standard Error 0.024	0.393 litre Standard Error 0.023

SECONDARY outcome

Timeframe: 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.

Individual Forced expiratory volume in one second (FEV1) values measured at each time points at Week 0, 4, 12, and 24 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 0 - 15 minutes (min)	1.200 litre Standard Error 0.006	1.309 litre Standard Error 0.006	1.310 litre Standard Error 0.006	1.263 litre Standard Error 0.006	1.276 litre Standard Error 0.006
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 0 - 30 min	1.206 litre Standard Error 0.007	1.347 litre Standard Error 0.007	1.357 litre Standard Error 0.007	1.318 litre Standard Error 0.007	1.311 litre Standard Error 0.007
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 0 - 1 hour (h)	1.223 litre Standard Error 0.008	1.375 litre Standard Error 0.008	1.390 litre Standard Error 0.008	1.369 litre Standard Error 0.008	1.353 litre Standard Error 0.008
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 0 - 2 h	1.212 litre Standard Error 0.008	1.373 litre Standard Error 0.008	1.388 litre Standard Error 0.008	1.395 litre Standard Error 0.008	1.378 litre Standard Error 0.008
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 0 - 3 h	1.220 litre Standard Error 0.009	1.363 litre Standard Error 0.009	1.389 litre Standard Error 0.009	1.403 litre Standard Error 0.009	1.388 litre Standard Error 0.009
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 0 min	1.163 litre Standard Error 0.009	1.249 litre Standard Error 0.009	1.274 litre Standard Error 0.009	1.284 litre Standard Error 0.009	1.283 litre Standard Error 0.009
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 15 min	1.187 litre Standard Error 0.010	1.319 litre Standard Error 0.010	1.321 litre Standard Error 0.010	1.279 litre Standard Error 0.010	1.348 litre Standard Error 0.010
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 30 min	1.200 litre Standard Error 0.010	1.346 litre Standard Error 0.010	1.346 litre Standard Error 0.011	1.308 litre Standard Error 0.011	1.374 litre Standard Error 0.010
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 1 h	1.207 litre Standard Error 0.011	1.360 litre Standard Error 0.011	1.366 litre Standard Error 0.011	1.350 litre Standard Error 0.011	1.397 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 2 h	1.211 litre Standard Error 0.011	1.360 litre Standard Error 0.011	1.372 litre Standard Error 0.011	1.372 litre Standard Error 0.011	1.401 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 4 - 3 h	1.211 litre Standard Error 0.011	1.355 litre Standard Error 0.011	1.368 litre Standard Error 0.011	1.380 litre Standard Error 0.012	1.401 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 0 min	1.174 litre Standard Error 0.010	1.249 litre Standard Error 0.010	1.267 litre Standard Error 0.010	1.291 litre Standard Error 0.010	1.293 litre Standard Error 0.010
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 15 min	1.188 litre Standard Error 0.011	1.321 litre Standard Error 0.011	1.313 litre Standard Error 0.011	1.292 litre Standard Error 0.011	1.354 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 30 min	1.196 litre Standard Error 0.011	1.348 litre Standard Error 0.011	1.335 litre Standard Error 0.011	1.313 litre Standard Error 0.011	1.371 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 1 h	1.209 litre Standard Error 0.011	1.358 litre Standard Error 0.011	1.356 litre Standard Error 0.011	1.345 litre Standard Error 0.011	1.391 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 2 h	1.205 litre Standard Error 0.011	1.357 litre Standard Error 0.011	1.365 litre Standard Error 0.011	1.372 litre Standard Error 0.012	1.401 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 12 - 3 h	1.205 litre Standard Error 0.011	1.352 litre Standard Error 0.012	1.363 litre Standard Error 0.012	1.384 litre Standard Error 0.012	1.401 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 - 0 min	1.150 litre Standard Error 0.010	1.227 litre Standard Error 0.010	1.250 litre Standard Error 0.011	1.270 litre Standard Error 0.011	1.276 litre Standard Error 0.010
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 0:15 min	1.164 litre Standard Error 0.011	1.297 litre Standard Error 0.011	1.298 litre Standard Error 0.011	1.278 litre Standard Error 0.012	1.326 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 - 30 min	1.170 litre Standard Error 0.011	1.318 litre Standard Error 0.012	1.320 litre Standard Error 0.012	1.296 litre Standard Error 0.012	1.355 litre Standard Error 0.011
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 - 1 h	1.180 litre Standard Error 0.012	1.338 litre Standard Error 0.012	1.342 litre Standard Error 0.012	1.331 litre Standard Error 0.012	1.368 litre Standard Error 0.012
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 - 2 h	1.180 litre Standard Error 0.012	1.332 litre Standard Error 0.012	1.345 litre Standard Error 0.012	1.346 litre Standard Error 0.012	1.373 litre Standard Error 0.012
Individual Forced Expiratory Volume in One Second (FEV1) Measurements at Each Time Point Week 24 - 3 h	1.180 litre Standard Error 0.012	1.326 litre Standard Error 0.012	1.344 litre Standard Error 0.012	1.357 litre Standard Error 0.012	1.370 litre Standard Error 0.012

SECONDARY outcome

Timeframe: 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.

Individual Forced Vital Capacity (FVC) values measured at each time point at Week 0, 4, 12, and 24 were reported.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 0 - 30 min	2.589 litre Standard Error 0.015	2.854 litre Standard Error 0.015	2.852 litre Standard Error 0.015	2.776 litre Standard Error 0.016	2.802 litre Standard Error 0.015
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 0 - 1 hour (h)	2.617 litre Standard Error 0.016	2.885 litre Standard Error 0.017	2.907 litre Standard Error 0.017	2.853 litre Standard Error 0.017	2.864 litre Standard Error 0.016
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 0 - 2 h	2.598 litre Standard Error 0.017	2.881 litre Standard Error 0.017	2.896 litre Standard Error 0.018	2.886 litre Standard Error 0.018	2.885 litre Standard Error 0.017
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 0 - 3 h	2.617 litre Standard Error 0.019	2.867 litre Standard Error 0.019	2.896 litre Standard Error 0.019	2.896 litre Standard Error 0.019	2.901 litre Standard Error 0.019
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 0 minutes	2.510 litre Standard Error 0.016	2.665 litre Standard Error 0.016	2.689 litre Standard Error 0.016	2.688 litre Standard Error 0.017	2.702 litre Standard Error 0.016
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 15 minutes	2.547 litre Standard Error 0.019	2.770 litre Standard Error 0.019	2.776 litre Standard Error 0.019	2.670 litre Standard Error 0.019	2.822 litre Standard Error 0.019
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 30 min	2.575 litre Standard Error 0.020	2.812 litre Standard Error 0.020	2.803 litre Standard Error 0.020	2.711 litre Standard Error 0.020	2.852 litre Standard Error 0.020
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 1 h	2.590 litre Standard Error 0.020	2.842 litre Standard Error 0.020	2.848 litre Standard Error 0.021	2.779 litre Standard Error 0.021	2.891 litre Standard Error 0.020
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 2 h	2.592 litre Standard Error 0.021	2.842 litre Standard Error 0.021	2.851 litre Standard Error 0.021	2.815 litre Standard Error 0.022	2.893 litre Standard Error 0.021
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 4 - 3 h	2.595 litre Standard Error 0.021	2.842 litre Standard Error 0.021	2.849 litre Standard Error 0.022	2.837 litre Standard Error 0.022	2.891 litre Standard Error 0.021
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 0 min	2.533 litre Standard Error 0.018	2.654 litre Standard Error 0.018	2.687 litre Standard Error 0.018	2.703 litre Standard Error 0.018	2.711 litre Standard Error 0.018
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 15 min	2.563 litre Standard Error 0.020	2.764 litre Standard Error 0.020	2.751 litre Standard Error 0.020	2.688 litre Standard Error 0.021	2.803 litre Standard Error 0.020
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 30 minutes	2.574 litre Standard Error 0.020	2.796 litre Standard Error 0.020	2.788 litre Standard Error 0.021	2.720 litre Standard Error 0.021	2.844 litre Standard Error 0.020
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 1 h	2.606 litre Standard Error 0.021	2.823 litre Standard Error 0.021	2.821 litre Standard Error 0.022	2.773 litre Standard Error 0.022	2.866 litre Standard Error 0.021
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 2 h	2.584 litre Standard Error 0.022	2.828 litre Standard Error 0.022	2.829 litre Standard Error 0.022	2.820 litre Standard Error 0.023	2.878 litre Standard Error 0.022
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 12 - 3 h	2.588 litre Standard Error 0.022	2.819 litre Standard Error 0.022	2.836 litre Standard Error 0.022	2.840 litre Standard Error 0.023	2.886 litre Standard Error 0.022
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24 - 0 min	2.489 litre Standard Error 0.019	2.614 litre Standard Error 0.019	2.637 litre Standard Error 0.019	2.664 litre Standard Error 0.020	2.678 litre Standard Error 0.019
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24 - 15 min	2.504 litre Standard Error 0.021	2.725 litre Standard Error 0.021	2.705 litre Standard Error 0.021	2.667 litre Standard Error 0.022	2.761 litre Standard Error 0.021
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24- 30 min	2.520 litre Standard Error 0.022	2.753 litre Standard Error 0.022	2.724 litre Standard Error 0.022	2.690 litre Standard Error 0.022	2.803 litre Standard Error 0.022
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24 - 1 h	2.539 litre Standard Error 0.022	2.793 litre Standard Error 0.022	2.763 litre Standard Error 0.022	2.739 litre Standard Error 0.023	2.823 litre Standard Error 0.022
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24 - 2 h	2.533 litre Standard Error 0.023	2.778 litre Standard Error 0.023	2.770 litre Standard Error 0.023	2.771 litre Standard Error 0.023	2.822 litre Standard Error 0.022
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 24 - 3 h	2.547 litre Standard Error 0.023	2.769 litre Standard Error 0.024	2.766 litre Standard Error 0.024	2.789 litre Standard Error 0.024	2.806 litre Standard Error 0.023
Individual Forced Vital Capacity (FVC) Measurements at Each Time Point Week 0 - 15 minutes (min)	2.572 litre Standard Error 0.013	2.787 litre Standard Error 0.013	2.778 litre Standard Error 0.013	2.691 litre Standard Error 0.013	2.729 litre Standard Error 0.013

SECONDARY outcome

Timeframe: 40 minutes (min) and 15 min before drug administration at Day 1 (baseline) and Day 3 and 5 of treatment period.

Population: Sub-study set (SUB): This patient set includes all patients in the full analysis set that were enrolled in the sub-study (at selected sites only) and have acceptable non-missing forced expiratory volume in one second (FEV1) data from 2 additional visits 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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=58 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=56 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=54 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=53 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Trough Forced Expiratory Volume in One Second (FEV1) Response on Day 3 and 5 Day 3	0.008 liter Standard Error 0.026	0.060 liter Standard Error 0.025	0.101 liter Standard Error 0.025	0.124 liter Standard Error 0.026	0.103 liter Standard Error 0.026
Trough Forced Expiratory Volume in One Second (FEV1) Response on Day 3 and 5 Day 5	0.012 liter Standard Error 0.023	0.041 liter Standard Error 0.023	0.095 liter Standard Error 0.023	0.115 liter Standard Error 0.24	0.118 liter Standard Error 0.024

SECONDARY outcome

Timeframe: 3 minutes (min) and 10 after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24.

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.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=58 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=56 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=54 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=53 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 0 - 3 minutes (min)	1.128 litre Standard Error 0.015	1.195 litre Standard Error 0.015	1.185 litre Standard Error 0.015	1.147 litre Standard Error 0.015	1.206 litre Standard Error 0.016
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 0 -10 min	1.135 litre Standard Error 0.018	1.253 litre Standard Error 0.017	1.268 litre Standard Error 0.017	1.224 litre Standard Error 0.018	1.247 litre Standard Error 0.018
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 4 - 3 min	1.161 litre Standard Error 0.026	1.208 litre Standard Error 0.025	1.259 litre Standard Error 0.025	1.227 litre Standard Error 0.026	1.260 litre Standard Error 0.026
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 4 - 10 min	1.160 litre Standard Error 0.028	1.252 litre Standard Error 0.027	1.312 litre Standard Error 0.028	1.252 litre Standard Error 0.028	1.301 litre Standard Error 0.029
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 12 - 3 min	1.151 litre Standard Error 0.028	1.233 litre Standard Error 0.027	1.251 litre Standard Error 0.027	1.258 litre Standard Error 0.028	1.310 litre Standard Error 0.028
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 12 - 10 min	1.172 litre Standard Error 0.027	1.258 litre Standard Error 0.027	1.304 litre Standard Error 0.027	1.279 litre Standard Error 0.027	1.336 litre Standard Error 0.028
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 24 - 3 min	1.115 litre Standard Error 0.029	1.196 litre Standard Error 0.029	1.230 litre Standard Error 0.029	1.211 litre Standard Error 0.030	1.301 litre Standard Error 0.030
Forced Expiratory Volume in One Second (FEV1) at 3 Minutes and 10 Minutes Following Drug Administration Week 24 - 10 min	1.138 litre Standard Error 0.032	1.240 litre Standard Error 0.031	1.278 litre Standard Error 0.031	1.244 litre Standard Error 0.032	1.329 litre Standard Error 0.032

SECONDARY outcome

Timeframe: 3 minutes (min) and 10 min after drug administration at Week 0 (Day 1 of treatment period), 4, 12, and 24.

Forced Vital Capacity (FVC) values at 3 minutes and 10 minutes following drug administration at Week 0, 4, 12, and 24 are reported.

Outcome measures

Outcome measures
Measure	Placebo n=55 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=58 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=56 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=54 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=53 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 12 - 3 min	2.395 litre Standard Error 0.048	2.594 litre Standard Error 0.047	2.604 litre Standard Error 0.048	2.549 litre Standard Error 0.049	2.631 litre Standard Error 0.049
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 0 - 3 minutes (min)	2.381 litre Standard Error 0.028	2.530 litre Standard Error 0.027	2.535 litre Standard Error 0.027	2.455 litre Standard Error 0.028	2.500 litre Standard Error 0.028
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 0 - 10 min	2.392 litre Standard Error 0.034	2.624 litre Standard Error 0.033	2.658 litre Standard Error 0.033	2.557 litre Standard Error 0.034	2.593 litre Standard Error 0.034
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 4 - 3 min	2.391 litre Standard Error 0.044	2.623 litre Standard Error 0.043	2.638 litre Standard Error 0.044	2.523 litre Standard Error 0.044	2.601 litre Standard Error 0.045
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 4 - 10 min	2.391 litre Standard Error 0.049	2.693 litre Standard Error 0.048	2.697 litre Standard Error 0.048	2.540 litre Standard Error 0.049	2.634 litre Standard Error 0.050
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 12 - 10 min	2.417 litre Standard Error 0.050	2.648 litre Standard Error 0.049	2.637 litre Standard Error 0.049	2.579 litre Standard Error 0.050	2.646 litre Standard Error 0.051
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 24 - 3 min	2.355 litre Standard Error 0.054	2.566 litre Standard Error 0.053	2.556 litre Standard Error 0.053	2.513 litre Standard Error 0.054	2.624 litre Standard Error 0.055
Forced Vital Capacity (FVC) at 3 Minutes and 10 Minutes Following Drug Administration Week 24 - 10 min	2.403 litre Standard Error 0.058	2.635 litre Standard Error 0.057	2.599 litre Standard Error 0.057	2.545 litre Standard Error 0.058	2.664 litre Standard Error 0.059

SECONDARY outcome

Timeframe: Assessed before drug administration per day during 24 weeks with weekly mean values reporting.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 1	163.41 litres/minute Standard Error 1.629	177.03 litres/minute Standard Error 1.641	176.20 litres/minute Standard Error 1.658	179.46 litres/minute Standard Error 1.718	177.54 litres/minute Standard Error 1.628
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 2	164.34 litres/minute Standard Error 1.917	177.64 litres/minute Standard Error 1.932	175.82 litres/minute Standard Error 1.952	179.24 litres/minute Standard Error 2.023	176.46 litres/minute Standard Error 1.916
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 3	164.53 litres/minute Standard Error 1.957	177.19 litres/minute Standard Error 1.972	177.38 litres/minute Standard Error 1.993	178.94 litres/minute Standard Error 2.067	175.49 litres/minute Standard Error 1.956
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 4	163.82 litres/minute Standard Error 2.006	174.99 litres/minute Standard Error 2.021	176.37 litres/minute Standard Error 2.042	178.06 litres/minute Standard Error 2.118	175.17 litres/minute Standard Error 2.004
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 5	163.00 litres/minute Standard Error 1.983	176.16 litres/minute Standard Error 1.998	176.90 litres/minute Standard Error 2.019	178.29 litres/minute Standard Error 2.094	176.32 litres/minute Standard Error 1.982
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 6	162.31 litres/minute Standard Error 2.058	176.26 litres/minute Standard Error 2.073	175.31 litres/minute Standard Error 2.095	177.59 litres/minute Standard Error 2.172	175.09 litres/minute Standard Error 2.056
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 7	160.30 litres/minute Standard Error 2.033	175.71 litres/minute Standard Error 2.049	174.35 litres/minute Standard Error 2.070	175.85 litres/minute Standard Error 2.147	175.50 litres/minute Standard Error 2.032
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 8	159.83 litres/minute Standard Error 2.085	173.99 litres/minute Standard Error 2.101	173.95 litres/minute Standard Error 2.123	176.41 litres/minute Standard Error 2.201	174.71 litres/minute Standard Error 2.084
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 9	159.89 litres/minute Standard Error 2.156	175.74 litres/minute Standard Error 2.171	172.84 litres/minute Standard Error 2.194	177.35 litres/minute Standard Error 2.274	174.75 litres/minute Standard Error 2.154
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 10	158.74 litres/minute Standard Error 2.126	173.63 litres/minute Standard Error 2.142	171.24 litres/minute Standard Error 2.164	176.14 litres/minute Standard Error 2.242	174.71 litres/minute Standard Error 2.125
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 11	157.98 litres/minute Standard Error 2.165	173.45 litres/minute Standard Error 2.181	169.92 litres/minute Standard Error 2.204	174.05 litres/minute Standard Error 2.283	174.82 litres/minute Standard Error 2.163
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 12	156.91 litres/minute Standard Error 2.192	174.72 litres/minute Standard Error 2.209	169.90 litres/minute Standard Error 2.232	175.40 litres/minute Standard Error 2.316	174.63 litres/minute Standard Error 2.191
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 13	156.22 litres/minute Standard Error 2.093	173.59 litres/minute Standard Error 2.109	169.96 litres/minute Standard Error 2.131	175.51 litres/minute Standard Error 2.211	175.97 litres/minute Standard Error 2.091
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 14	156.66 litres/minute Standard Error 2.165	172.29 litres/minute Standard Error 2.181	168.51 litres/minute Standard Error 2.203	175.65 litres/minute Standard Error 2.283	174.86 litres/minute Standard Error 2.163
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 15	156.78 litres/minute Standard Error 2.196	171.12 litres/minute Standard Error 2.213	168.69 litres/minute Standard Error 2.236	175.01 litres/minute Standard Error 2.318	174.03 litres/minute Standard Error 2.195
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 16	155.76 litres/minute Standard Error 2.206	170.92 litres/minute Standard Error 2.223	169.26 litres/minute Standard Error 2.246	174.07 litres/minute Standard Error 2.330	174.23 litres/minute Standard Error 2.205
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 17	154.59 litres/minute Standard Error 2.267	171.32 litres/minute Standard Error 2.285	169.53 litres/minute Standard Error 2.309	174.89 litres/minute Standard Error 2.396	174.04 litres/minute Standard Error 2.266
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 18	154.04 litres/minute Standard Error 2.248	169.36 litres/minute Standard Error 2.266	168.95 litres/minute Standard Error 2.289	173.59 litres/minute Standard Error 2.376	171.90 litres/minute Standard Error 2.246
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 19	154.37 litres/minute Standard Error 2.263	169.24 litres/minute Standard Error 2.280	170.45 litres/minute Standard Error 2.304	175.29 litres/minute Standard Error 2.389	172.92 litres/minute Standard Error 2.261
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 20	154.77 litres/minute Standard Error 2.291	169.31 litres/minute Standard Error 2.309	169.84 litres/minute Standard Error 2.332	174.81 litres/minute Standard Error 2.420	173.31 litres/minute Standard Error 2.289
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 21	153.47 litres/minute Standard Error 2.276	169.30 litres/minute Standard Error 2.293	169.12 litres/minute Standard Error 2.317	175.43 litres/minute Standard Error 2.404	172.77 litres/minute Standard Error 2.274
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 22	153.85 litres/minute Standard Error 2.267	167.60 litres/minute Standard Error 2.284	169.29 litres/minute Standard Error 2.308	175.12 litres/minute Standard Error 2.393	171.93 litres/minute Standard Error 2.265
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 23	153.41 litres/minute Standard Error 2.303	167.38 litres/minute Standard Error 2.320	167.26 litres/minute Standard Error 2.345	174.30 litres/minute Standard Error 2.430	171.13 litres/minute Standard Error 2.302
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEFR) Week 24	153.15 litres/minute Standard Error 2.311	167.08 litres/minute Standard Error 2.329	165.87 litres/minute Standard Error 2.353	176.36 litres/minute Standard Error 2.441	171.53 litres/minute Standard Error 2.310

SECONDARY outcome

Timeframe: Assessed at bed time per day during 24 weeks with weekly mean values reporting.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 1	173.64 litres/minute Standard Error 1.467	186.40 litres/minute Standard Error 1.463	186.37 litres/minute Standard Error 1.467	187.31 litres/minute Standard Error 1.542	187.13 litres/minute Standard Error 1.446
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 2	173.18 litres/minute Standard Error 1.694	187.16 litres/minute Standard Error 1.690	185.96 litres/minute Standard Error 1.694	187.16 litres/minute Standard Error 1.782	185.79 litres/minute Standard Error 1.669
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 3	171.85 litres/minute Standard Error 1.761	187.14 litres/minute Standard Error 1.756	183.77 litres/minute Standard Error 1.761	187.41 litres/minute Standard Error 1.851	185.61 litres/minute Standard Error 1.735
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 4	170.91 litres/minute Standard Error 1.858	186.96 litres/minute Standard Error 1.853	184.33 litres/minute Standard Error 1.858	187.11 litres/minute Standard Error 1.952	185.23 litres/minute Standard Error 1.831
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 5	172.33 litres/minute Standard Error 1.921	186.03 litres/minute Standard Error 1.915	186.84 litres/minute Standard Error 1.920	185.67 litres/minute Standard Error 2.017	185.02 litres/minute Standard Error 1.893
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 6	169.29 litres/minute Standard Error 2.009	183.97 litres/minute Standard Error 2.004	185.32 litres/minute Standard Error 2.009	184.51 litres/minute Standard Error 2.110	184.34 litres/minute Standard Error 1.980
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 7	168.10 litres/minute Standard Error 1.989	183.82 litres/minute Standard Error 1.984	184.57 litres/minute Standard Error 1.989	182.39 litres/minute Standard Error 2.090	183.80 litres/minute Standard Error 1.960
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 8	166.98 litres/minute Standard Error 1.975	183.69 litres/minute Standard Error 1.970	182.81 litres/minute Standard Error 1.975	182.01 litres/minute Standard Error 2.076	181.66 litres/minute Standard Error 1.947
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 9	165.67 litres/minute Standard Error 2.033	182.98 litres/minute Standard Error 2.028	181.88 litres/minute Standard Error 2.033	184.21 litres/minute Standard Error 2.136	183.38 litres/minute Standard Error 2.004
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 10	164.15 litres/minute Standard Error 2.067	181.90 litres/minute Standard Error 2.062	179.46 litres/minute Standard Error 2.067	182.53 litres/minute Standard Error 2.170	182.12 litres/minute Standard Error 2.038
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 11	163.02 litres/minute Standard Error 2.122	182.05 litres/minute Standard Error 2.117	179.36 litres/minute Standard Error 2.122	182.54 litres/minute Standard Error 2.227	181.58 litres/minute Standard Error 2.092
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 12	163.84 litres/minute Standard Error 2.169	180.46 litres/minute Standard Error 2.163	179.65 litres/minute Standard Error 2.169	180.52 litres/minute Standard Error 2.281	181.09 litres/minute Standard Error 2.138
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 13	163.95 litres/minute Standard Error 2.162	180.80 litres/minute Standard Error 2.156	178.40 litres/minute Standard Error 2.162	181.12 litres/minute Standard Error 2.270	183.50 litres/minute Standard Error 2.131
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 14	162.72 litres/minute Standard Error 2.168	179.23 litres/minute Standard Error 2.162	177.70 litres/minute Standard Error 2.168	181.26 litres/minute Standard Error 2.278	183.27 litres/minute Standard Error 2.137
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 15	162.77 litres/minute Standard Error 2.193	178.86 litres/minute Standard Error 2.187	177.33 litres/minute Standard Error 2.193	181.66 litres/minute Standard Error 2.304	182.12 litres/minute Standard Error 2.162
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 16	161.50 litres/minute Standard Error 2.227	179.17 litres/minute Standard Error 2.220	177.30 litres/minute Standard Error 2.226	180.18 litres/minute Standard Error 2.342	180.76 litres/minute Standard Error 2.194
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 17	161.12 litres/minute Standard Error 2.199	179.50 litres/minute Standard Error 2.193	177.51 litres/minute Standard Error 2.198	178.95 litres/minute Standard Error 2.314	180.40 litres/minute Standard Error 2.167
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 18	161.66 litres/minute Standard Error 2.206	177.88 litres/minute Standard Error 2.200	176.28 litres/minute Standard Error 2.206	178.92 litres/minute Standard Error 2.321	179.47 litres/minute Standard Error 2.174
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 19	161.70 litres/minute Standard Error 2.229	177.34 litres/minute Standard Error 2.223	177.78 litres/minute Standard Error 2.229	178.64 litres/minute Standard Error 2.342	179.98 litres/minute Standard Error 2.197
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 20	160.54 litres/minute Standard Error 2.322	177.50 litres/minute Standard Error 2.316	177.23 litres/minute Standard Error 2.322	179.20 litres/minute Standard Error 2.441	180.70 litres/minute Standard Error 2.288
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 21	161.13 litres/minute Standard Error 2.307	175.87 litres/minute Standard Error 2.300	176.16 litres/minute Standard Error 2.306	178.87 litres/minute Standard Error 2.424	179.66 litres/minute Standard Error 2.273
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 22	160.32 litres/minute Standard Error 2.309	174.78 litres/minute Standard Error 2.302	175.23 litres/minute Standard Error 2.308	177.71 litres/minute Standard Error 2.424	178.98 litres/minute Standard Error 2.275
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 23	160.75 litres/minute Standard Error 2.316	174.37 litres/minute Standard Error 2.310	176.10 litres/minute Standard Error 2.316	177.54 litres/minute Standard Error 2.434	178.20 litres/minute Standard Error 2.283
Weekly Mean Evening Peak Expiratory Flow Rate (PEFR) Week 24	159.69 litres/minute Standard Error 2.356	172.72 litres/minute Standard Error 2.349	176.20 litres/minute Standard Error 2.356	179.04 litres/minute Standard Error 2.475	178.21 litres/minute Standard Error 2.322

SECONDARY outcome

Timeframe: Assessed once per day during 24 weeks with weekly mean values reporting.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 1	2.514 Metered Dose Inhaler use per day Standard Error 0.075	1.964 Metered Dose Inhaler use per day Standard Error 0.075	1.972 Metered Dose Inhaler use per day Standard Error 0.076	1.790 Metered Dose Inhaler use per day Standard Error 0.078	2.084 Metered Dose Inhaler use per day Standard Error 0.075
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 2	2.524 Metered Dose Inhaler use per day Standard Error 0.079	1.985 Metered Dose Inhaler use per day Standard Error 0.079	2.044 Metered Dose Inhaler use per day Standard Error 0.080	1.803 Metered Dose Inhaler use per day Standard Error 0.082	2.109 Metered Dose Inhaler use per day Standard Error 0.079
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 3	2.509 Metered Dose Inhaler use per day Standard Error 0.081	1.960 Metered Dose Inhaler use per day Standard Error 0.081	2.037 Metered Dose Inhaler use per day Standard Error 0.081	1.835 Metered Dose Inhaler use per day Standard Error 0.084	2.093 Metered Dose Inhaler use per day Standard Error 0.080
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 4	2.498 Metered Dose Inhaler use per day Standard Error 0.081	1.977 Metered Dose Inhaler use per day Standard Error 0.081	2.017 Metered Dose Inhaler use per day Standard Error 0.082	1.885 Metered Dose Inhaler use per day Standard Error 0.085	2.118 Metered Dose Inhaler use per day Standard Error 0.081
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 5	2.548 Metered Dose Inhaler use per day Standard Error 0.086	2.040 Metered Dose Inhaler use per day Standard Error 0.085	2.012 Metered Dose Inhaler use per day Standard Error 0.086	1.768 Metered Dose Inhaler use per day Standard Error 0.089	2.106 Metered Dose Inhaler use per day Standard Error 0.085
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 6	2.629 Metered Dose Inhaler use per day Standard Error 0.088	2.048 Metered Dose Inhaler use per day Standard Error 0.088	2.041 Metered Dose Inhaler use per day Standard Error 0.088	1.789 Metered Dose Inhaler use per day Standard Error 0.091	2.116 Metered Dose Inhaler use per day Standard Error 0.087
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 7	2.656 Metered Dose Inhaler use per day Standard Error 0.088	2.042 Metered Dose Inhaler use per day Standard Error 0.088	2.039 Metered Dose Inhaler use per day Standard Error 0.088	1.851 Metered Dose Inhaler use per day Standard Error 0.091	2.122 Metered Dose Inhaler use per day Standard Error 0.087
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 8	2.612 Metered Dose Inhaler use per day Standard Error 0.089	2.007 Metered Dose Inhaler use per day Standard Error 0.088	2.010 Metered Dose Inhaler use per day Standard Error 0.089	1.877 Metered Dose Inhaler use per day Standard Error 0.092	2.129 Metered Dose Inhaler use per day Standard Error 0.088
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 9	2.617 Metered Dose Inhaler use per day Standard Error 0.088	2.026 Metered Dose Inhaler use per day Standard Error 0.088	1.981 Metered Dose Inhaler use per day Standard Error 0.089	1.834 Metered Dose Inhaler use per day Standard Error 0.092	2.094 Metered Dose Inhaler use per day Standard Error 0.088
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 10	2.623 Metered Dose Inhaler use per day Standard Error 0.090	2.062 Metered Dose Inhaler use per day Standard Error 0.090	2.013 Metered Dose Inhaler use per day Standard Error 0.091	1.838 Metered Dose Inhaler use per day Standard Error 0.093	2.137 Metered Dose Inhaler use per day Standard Error 0.089
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 11	2.693 Metered Dose Inhaler use per day Standard Error 0.092	2.136 Metered Dose Inhaler use per day Standard Error 0.092	2.020 Metered Dose Inhaler use per day Standard Error 0.093	1.872 Metered Dose Inhaler use per day Standard Error 0.096	2.154 Metered Dose Inhaler use per day Standard Error 0.091
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 12	2.678 Metered Dose Inhaler use per day Standard Error 0.091	2.127 Metered Dose Inhaler use per day Standard Error 0.091	2.011 Metered Dose Inhaler use per day Standard Error 0.092	1.899 Metered Dose Inhaler use per day Standard Error 0.095	2.122 Metered Dose Inhaler use per day Standard Error 0.091
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 13	2.645 Metered Dose Inhaler use per day Standard Error 0.091	2.074 Metered Dose Inhaler use per day Standard Error 0.091	2.108 Metered Dose Inhaler use per day Standard Error 0.092	1.844 Metered Dose Inhaler use per day Standard Error 0.094	2.112 Metered Dose Inhaler use per day Standard Error 0.090
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 14	2.655 Metered Dose Inhaler use per day Standard Error 0.091	2.131 Metered Dose Inhaler use per day Standard Error 0.091	2.161 Metered Dose Inhaler use per day Standard Error 0.092	1.844 Metered Dose Inhaler use per day Standard Error 0.095	2.063 Metered Dose Inhaler use per day Standard Error 0.091
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 15	2.712 Metered Dose Inhaler use per day Standard Error 0.094	2.148 Metered Dose Inhaler use per day Standard Error 0.094	2.127 Metered Dose Inhaler use per day Standard Error 0.095	1.859 Metered Dose Inhaler use per day Standard Error 0.098	2.141 Metered Dose Inhaler use per day Standard Error 0.093
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 16	2.732 Metered Dose Inhaler use per day Standard Error 0.095	2.081 Metered Dose Inhaler use per day Standard Error 0.095	2.090 Metered Dose Inhaler use per day Standard Error 0.096	1.906 Metered Dose Inhaler use per day Standard Error 0.099	2.143 Metered Dose Inhaler use per day Standard Error 0.094
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 17	2.738 Metered Dose Inhaler use per day Standard Error 0.096	2.060 Metered Dose Inhaler use per day Standard Error 0.096	2.111 Metered Dose Inhaler use per day Standard Error 0.097	1.899 Metered Dose Inhaler use per day Standard Error 0.100	2.153 Metered Dose Inhaler use per day Standard Error 0.096
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 18	2.756 Metered Dose Inhaler use per day Standard Error 0.097	2.074 Metered Dose Inhaler use per day Standard Error 0.097	2.078 Metered Dose Inhaler use per day Standard Error 0.098	1.872 Metered Dose Inhaler use per day Standard Error 0.100	2.146 Metered Dose Inhaler use per day Standard Error 0.096
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 19	2.706 Metered Dose Inhaler use per day Standard Error 0.099	2.105 Metered Dose Inhaler use per day Standard Error 0.099	2.083 Metered Dose Inhaler use per day Standard Error 0.100	1.896 Metered Dose Inhaler use per day Standard Error 0.103	2.154 Metered Dose Inhaler use per day Standard Error 0.098
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 20	2.670 Metered Dose Inhaler use per day Standard Error 0.101	2.084 Metered Dose Inhaler use per day Standard Error 0.101	2.149 Metered Dose Inhaler use per day Standard Error 0.102	1.975 Metered Dose Inhaler use per day Standard Error 0.105	2.180 Metered Dose Inhaler use per day Standard Error 0.100
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 21	2.706 Metered Dose Inhaler use per day Standard Error 0.098	2.103 Metered Dose Inhaler use per day Standard Error 0.098	2.116 Metered Dose Inhaler use per day Standard Error 0.099	1.928 Metered Dose Inhaler use per day Standard Error 0.102	2.156 Metered Dose Inhaler use per day Standard Error 0.098
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 22	2.704 Metered Dose Inhaler use per day Standard Error 0.098	2.124 Metered Dose Inhaler use per day Standard Error 0.098	2.119 Metered Dose Inhaler use per day Standard Error 0.099	1.928 Metered Dose Inhaler use per day Standard Error 0.102	2.168 Metered Dose Inhaler use per day Standard Error 0.098
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 23	2.675 Metered Dose Inhaler use per day Standard Error 0.098	2.056 Metered Dose Inhaler use per day Standard Error 0.098	2.094 Metered Dose Inhaler use per day Standard Error 0.099	1.959 Metered Dose Inhaler use per day Standard Error 0.102	2.138 Metered Dose Inhaler use per day Standard Error 0.097
Weekly Mean Number of Occasions of Rescue Therapy Used Per Day (as Occasion Requires (PRN) Salbutamol [Albuterol]) Week 24	2.672 Metered Dose Inhaler use per day Standard Error 0.100	2.114 Metered Dose Inhaler use per day Standard Error 0.100	2.116 Metered Dose Inhaler use per day Standard Error 0.101	1.961 Metered Dose Inhaler use per day Standard Error 0.104	2.148 Metered Dose Inhaler use per day Standard Error 0.099

SECONDARY outcome

Timeframe: At Week 0, 4, 12, and 24.

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.

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Physician's Global Evaluation Week 0	4.4 Score on scale Standard Error 1.2	4.5 Score on scale Standard Error 1.2	4.5 Score on scale Standard Error 1.2	4.4 Score on scale Standard Error 1.2	4.5 Score on scale Standard Error 1.1
Physician's Global Evaluation Week 4	4.541 Score on scale Standard Error 0.042	4.714 Score on scale Standard Error 0.042	4.747 Score on scale Standard Error 0.042	4.807 Score on scale Standard Error 0.044	4.739 Score on scale Standard Error 0.042
Physician's Global Evaluation Week 12	4.582 Score on scale Standard Error 0.047	4.804 Score on scale Standard Error 0.047	4.790 Score on scale Standard Error 0.047	4.880 Score on scale Standard Error 0.048	4.816 Score on scale Standard Error 0.047
Physician's Global Evaluation Week 24	4.613 Score on scale Standard Error 0.053	4.865 Score on scale Standard Error 0.053	4.775 Score on scale Standard Error 0.054	4.888 Score on scale Standard Error 0.055	4.810 Score on scale Standard Error 0.053

SECONDARY outcome

Timeframe: At Week 0 (baseline), 4, 12 and 24.

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).

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Transition Dyspnea Index - Functional Impairment Domain Score Week 0	2.3 Score on a scale Standard Error 0.9	2.3 Score on a scale Standard Error 0.9	2.3 Score on a scale Standard Error 0.9	2.2 Score on a scale Standard Error 0.9	2.3 Score on a scale Standard Error 0.9
Transition Dyspnea Index - Functional Impairment Domain Score Week 4	0.192 Score on a scale Standard Error 0.048	0.379 Score on a scale Standard Error 0.048	0.480 Score on a scale Standard Error 0.049	0.518 Score on a scale Standard Error 0.050	0.462 Score on a scale Standard Error 0.048
Transition Dyspnea Index - Functional Impairment Domain Score Week 12	0.276 Score on a scale Standard Error 0.052	0.474 Score on a scale Standard Error 0.052	0.519 Score on a scale Standard Error 0.053	0.454 Score on a scale Standard Error 0.054	0.492 Score on a scale Standard Error 0.052
Transition Dyspnea Index - Functional Impairment Domain Score Week 24	0.353 Score on a scale Standard Error 0.054	0.465 Score on a scale Standard Error 0.054	0.445 Score on a scale Standard Error 0.055	0.465 Score on a scale Standard Error 0.056	0.488 Score on a scale Standard Error 0.054

SECONDARY outcome

Timeframe: At week 0 (baseline), 4, 12 and 24

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Transition Dyspnea Index - Magnitude of Task Domain Score Week 0	2.2 Score on a scale Standard Error 0.8	2.2 Score on a scale Standard Error 0.8	2.2 Score on a scale Standard Error 0.8	2.2 Score on a scale Standard Error 0.8	2.2 Score on a scale Standard Error 0.7
Transition Dyspnea Index - Magnitude of Task Domain Score Week 4	0.245 Score on a scale Standard Error 0.048	0.494 Score on a scale Standard Error 0.048	0.538 Score on a scale Standard Error 0.049	0.571 Score on a scale Standard Error 0.050	0.489 Score on a scale Standard Error 0.048
Transition Dyspnea Index - Magnitude of Task Domain Score Week 12	0.282 Score on a scale Standard Error 0.053	0.494 Score on a scale Standard Error 0.053	0.587 Score on a scale Standard Error 0.053	0.479 Score on a scale Standard Error 0.054	0.523 Score on a scale Standard Error 0.053
Transition Dyspnea Index - Magnitude of Task Domain Score Week 24	0.322 Score on a scale Standard Error 0.055	0.510 Score on a scale Standard Error 0.055	0.513 Score on a scale Standard Error 0.056	0.514 Score on a scale Standard Error 0.057	0.496 Score on a scale Standard Error 0.055

SECONDARY outcome

Timeframe: At Week 0 (baseline), 4, 12 and 24

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).

Outcome measures

Outcome measures
Measure	Placebo n=421 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=417 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=409 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=387 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=423 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
Transition Dyspnea Index - Magnitude of Effort Domain Score Week 0	2.1 Score on a scale Standard Error 0.7	2.0 Score on a scale Standard Error 0.8	2.0 Score on a scale Standard Error 0.8	2.0 Score on a scale Standard Error 0.7	2.0 Score on a scale Standard Error 0.7
Transition Dyspnea Index - Magnitude of Effort Domain Score Week 4	0.161 Score on a scale Standard Error 0.048	0.437 Score on a scale Standard Error 0.048	0.497 Score on a scale Standard Error 0.049	0.478 Score on a scale Standard Error 0.050	0.449 Score on a scale Standard Error 0.048
Transition Dyspnea Index - Magnitude of Effort Domain Score Week 12	0.253 Score on a scale Standard Error 0.054	0.423 Score on a scale Standard Error 0.054	0.486 Score on a scale Standard Error 0.054	0.460 Score on a scale Standard Error 0.055	0.478 Score on a scale Standard Error 0.053
Transition Dyspnea Index - Magnitude of Effort Domain Score Week 24	0.273 Score on a scale Standard Error 0.057	0.458 Score on a scale Standard Error 0.057	0.472 Score on a scale Standard Error 0.058	0.502 Score on a scale Standard Error 0.059	0.474 Score on a scale Standard Error 0.057

SECONDARY outcome

Timeframe: At Week 0, 4, 12, and 24.

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.

Outcome measures

Outcome measures
Measure	Placebo n=411 Participants Oral inhalation of solution of Placebo matching BEA 2180 BR was administered once daily via Respimat® inhaler for 24 weeks.	BEA 2180 BR 50 Microgram (mcg) n=415 Participants 2 oral inhalations of solution of 25 micrograms (mcg) of BEA 2180 BR (total: 50 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 100 Microgram (mcg) n=404 Participants 2 oral inhalations of solution of 50 micrograms (mcg) of BEA 2180 BR (total: 100 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	BEA 2180 BR 200 Microgram (mcg) n=379 Participants 2 oral inhalations of solution of 100 micrograms (mcg) of BEA 2180 BR (total: 200 mcg) were administered via Respimat® inhaler once daily for 24 weeks.	Tiotropium Bromide 5 Microgram (mcg) n=419 Participants 2 inhalation of solution of 2.5 micrograms (mcg) of Tiotropium Bromide (total: 5 mcg) were administered orally via Respimat® inhaler once daily for 24 weeks.
St. George's Respiratory Questionnaire (SGRQ) Total Score Week 0	43.2 Score on a scale Standard Deviation 18.1	41.9 Score on a scale Standard Deviation 17.5	42.5 Score on a scale Standard Deviation 17.7	43.8 Score on a scale Standard Deviation 18.8	43.1 Score on a scale Standard Deviation 17.8
St. George's Respiratory Questionnaire (SGRQ) Total Score Week 4	41.969 Score on a scale Standard Deviation 0.486	40.552 Score on a scale Standard Deviation 0.484	39.865 Score on a scale Standard Deviation 0.490	40.689 Score on a scale Standard Deviation 0.506	40.706 Score on a scale Standard Deviation 0.481
St. George's Respiratory Questionnaire (SGRQ) Total Score Week 12	42.744 Score on a scale Standard Deviation 0.575	40.293 Score on a scale Standard Deviation 0.573	39.506 Score on a scale Standard Deviation 0.580	40.368 Score on a scale Standard Deviation 0.596	39.489 Score on a scale Standard Deviation 0.570
St. George's Respiratory Questionnaire (SGRQ) Total Score Week 24	42.993 Score on a scale Standard Deviation 0.626	40.103 Score on a scale Standard Deviation 0.624	40.058 Score on a scale Standard Deviation 0.632	40.728 Score on a scale Standard Deviation 0.651	39.547 Score on a scale Standard Deviation 0.621

SECONDARY outcome

Timeframe: At baseline (Week 0, Day 1 of treatment period).

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.