Trial Outcomes & Findings for Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II (NCT NCT00796653)

Last Updated: 2014-06-27

Results Overview

Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

937 participants

Primary outcome timeframe

1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Results posted on

2014-06-27

Participant Flow

Three patients were randomized but not treated due to withdrawn consent and findings on pre-dose ECG prior to receiving study medication.

Participant milestones

Participant milestones
Measure	Placebo Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Study STARTED	235	232	234	233
Overall Study COMPLETED	184	195	198	193
Overall Study NOT COMPLETED	51	37	36	40

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Overall Study Adverse Event	19	16	16	16
Overall Study Lost to Follow-up	2	1	2	3
Overall Study Withdrawal by Subject	16	8	8	13
Overall Study Lack of Efficacy	8	1	3	2
Overall Study Non compliance with protocol	2	2	0	2
Overall Study Other reason not described above	4	9	7	4

Baseline Characteristics

Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease II

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=235 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=232 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=234 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Total n=934 Participants Total of all reporting groups
Age, Continuous	63.9 years STANDARD_DEVIATION 7.8 • n=5 Participants	63.7 years STANDARD_DEVIATION 8.8 • n=7 Participants	63.8 years STANDARD_DEVIATION 8.5 • n=5 Participants	65.0 years STANDARD_DEVIATION 8.2 • n=4 Participants	64.183 years STANDARD_DEVIATION 8.7 • n=21 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	45 Participants n=7 Participants	50 Participants n=5 Participants	41 Participants n=4 Participants	176 Participants n=21 Participants
Sex: Female, Male Male	195 Participants n=5 Participants	187 Participants n=7 Participants	184 Participants n=5 Participants	192 Participants n=4 Participants	758 Participants n=21 Participants
Tiotropium (Tio) Use Stratum Non-tiotropium	173 Number of participants n=5 Participants	174 Number of participants n=7 Participants	172 Number of participants n=5 Participants	174 Number of participants n=4 Participants	693 Number of participants n=21 Participants
Tiotropium (Tio) Use Stratum Tiotropium	62 Number of participants n=5 Participants	58 Number of participants n=7 Participants	62 Number of participants n=5 Participants	59 Number of participants n=4 Participants	241 Number of participants n=21 Participants

PRIMARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Population: Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks	-0.013 Liter Standard Error 0.014	0.116 Liter Standard Error 0.014	0.140 Liter Standard Error 0.014	0.137 Liter Standard Error 0.014	—	—	—	—

PRIMARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Population: FAS

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 24	-0.055 Liter Standard Error 0.014	-0.003 Liter Standard Error 0.014	0.014 Liter Standard Error 0.014	-0.013 Liter Standard Error 0.014	—	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 24

Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks	1.102 score on a scale Standard Error 0.229	1.504 score on a scale Standard Error 0.225	1.521 score on a scale Standard Error 0.225	1.703 score on a scale Standard Error 0.228	—	—	—	—

PRIMARY outcome

Timeframe: Baseline, Week 24

Population: Full analysis sets (FAS) of the trials NCT00793624 and NCT00796653. FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before 24 weeks for any of the co-primary efficacy variables.

This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).

Outcome measures

Outcome measures
Measure	Placebo n=413 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=433 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=427 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=417 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis	1.471 score on a scale Standard Error 0.155	1.980 score on a scale Standard Error 0.175	1.996 score on a scale Standard Error 0.170	1.827 score on a scale Standard Error 0.168	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=216 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=212 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=206 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks	42.120 score on a scale Standard Error 0.995	38.970 score on a scale Standard Error 0.965	38.597 score on a scale Standard Error 0.969	40.704 score on a scale Standard Error 0.984	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=216 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=212 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=206 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks	39.914 score on a scale Standard Error 1.022	39.562 score on a scale Standard Error 0.986	38.824 score on a scale Standard Error 0.991	40.025 score on a scale Standard Error 0.996	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=216 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=212 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=206 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks	42.679 score on a scale Standard Error 0.983	40.054 score on a scale Standard Error 0.955	40.190 score on a scale Standard Error 0.963	39.521 score on a scale Standard Error 0.975	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 24

Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model.

Outcome measures

Outcome measures
Measure	Placebo n=387 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=416 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=414 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=408 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis	41.639 score on a scale Standard Error 0.718	38.794 score on a scale Standard Error 0.693	38.205 score on a scale Standard Error 0.695	40.391 score on a scale Standard Error 0.699	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks	0.021 Liter Standard Error 0.013	0.181 Liter Standard Error 0.014	0.214 Liter Standard Error 0.013	0.183 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks	-0.010 Liter Standard Error 0.014	0.162 Liter Standard Error 0.014	0.181 Liter Standard Error 0.014	0.174 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks	-0.008 Liter Standard Error 0.014	0.138 Liter Standard Error 0.014	0.167 Liter Standard Error 0.014	0.163 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks	-0.025 Liter Standard Error 0.014	0.093 Liter Standard Error 0.014	0.116 Liter Standard Error 0.014	0.104 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 2	-0.016 Liter Standard Error 0.013	0.053 Liter Standard Error 0.013	0.103 Liter Standard Error 0.013	0.033 Liter Standard Error 0.013	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 6	-0.036 Liter Standard Error 0.013	0.047 Liter Standard Error 0.013	0.068 Liter Standard Error 0.013	0.034 Liter Standard Error 0.013	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 12	-0.041 Liter Standard Error 0.014	0.018 Liter Standard Error 0.013	0.052 Liter Standard Error 0.013	0.024 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 18	-0.036 Liter Standard Error 0.014	0.013 Liter Standard Error 0.014	0.049 Liter Standard Error 0.013	0.015 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 32	-0.039 Liter Standard Error 0.014	0.023 Liter Standard Error 0.014	0.034 Liter Standard Error 0.014	0.009 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 40	-0.043 Liter Standard Error 0.014	0.019 Liter Standard Error 0.014	0.041 Liter Standard Error 0.014	0.013 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FEV1 Response at Week 48	-0.060 Liter Standard Error 0.014	-0.016 Liter Standard Error 0.014	-0.001 Liter Standard Error 0.014	-0.024 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Response was defined as change from baseline. Baseline peak FEV1 was defined as the mean of the available pre-dose peak FEV1 values prior to first dose of randomized treatment. Peak FEV1 (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FEV1 (0-3h) Response After 2 Weeks	0.099 Liter Standard Error 0.014	0.260 Liter Standard Error 0.014	0.278 Liter Standard Error 0.014	0.253 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FEV1 (0-3h) Response After 6 Weeks	0.066 Liter Standard Error 0.014	0.235 Liter Standard Error 0.014	0.248 Liter Standard Error 0.014	0.242 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FEV1 (0-3h) Response After 12 Weeks	0.064 Liter Standard Error 0.014	0.206 Liter Standard Error 0.014	0.232 Liter Standard Error 0.014	0.228 Liter Standard Error 0.014	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FEV1 (0-3h) Response After 24 Weeks	0.060 Liter Standard Error 0.015	0.183 Liter Standard Error 0.014	0.211 Liter Standard Error 0.014	0.203 Liter Standard Error 0.015	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FEV1 (0-3h) Response After 48 Weeks	0.052 Liter Standard Error 0.015	0.163 Liter Standard Error 0.015	0.178 Liter Standard Error 0.015	0.170 Liter Standard Error 0.015	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks	0.082 Liter Standard Error 0.025	0.312 Liter Standard Error 0.025	0.332 Liter Standard Error 0.025	0.348 Liter Standard Error 0.025	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks	0.027 Liter Standard Error 0.025	0.277 Liter Standard Error 0.026	0.276 Liter Standard Error 0.025	0.307 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks	0.006 Liter Standard Error 0.026	0.235 Liter Standard Error 0.026	0.253 Liter Standard Error 0.026	0.280 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks	0.012 Liter Standard Error 0.026	0.212 Liter Standard Error 0.026	0.225 Liter Standard Error 0.026	0.253 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks	-0.036 Liter Standard Error 0.027	0.182 Liter Standard Error 0.026	0.201 Liter Standard Error 0.026	0.184 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Population: FAS

Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 2	0.030 Liter Standard Error 0.026	0.118 Liter Standard Error 0.026	0.173 Liter Standard Error 0.026	0.111 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 6	-0.014 Liter Standard Error 0.026	0.113 Liter Standard Error 0.026	0.101 Liter Standard Error 0.026	0.085 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 12	-0.041 Liter Standard Error 0.026	0.062 Liter Standard Error 0.026	0.062 Liter Standard Error 0.026	0.070 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 18	-0.014 Liter Standard Error 0.027	0.084 Liter Standard Error 0.026	0.107 Liter Standard Error 0.026	0.064 Liter Standard Error 0.026	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 24	-0.044 Liter Standard Error 0.027	0.023 Liter Standard Error 0.026	0.019 Liter Standard Error 0.026	-0.005 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 32	-0.007 Liter Standard Error 0.027	0.081 Liter Standard Error 0.027	0.063 Liter Standard Error 0.027	0.036 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 40	-0.016 Liter Standard Error 0.027	0.071 Liter Standard Error 0.027	0.105 Liter Standard Error 0.027	0.037 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=232 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=229 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=228 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=229 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Trough FVC Response at Week 48	-0.069 Liter Standard Error 0.027	0.012 Liter Standard Error 0.027	0.032 Liter Standard Error 0.027	-0.031 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks

Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FVC (0-3h) Response After 2 Weeks	0.247 Liter Standard Error 0.027	0.480 Liter Standard Error 0.027	0.476 Liter Standard Error 0.027	0.495 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FVC (0-3h) Response After 6 Weeks	0.196 Liter Standard Error 0.027	0.443 Liter Standard Error 0.027	0.417 Liter Standard Error 0.027	0.450 Liter Standard Error 0.027	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FVC (0-3h) Response After 12 Weeks	0.171 Liter Standard Error 0.028	0.386 Liter Standard Error 0.027	0.396 Liter Standard Error 0.027	0.436 Liter Standard Error 0.028	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FVC (0-3h) Response After 24 Weeks	0.189 Liter Standard Error 0.028	0.371 Liter Standard Error 0.028	0.369 Liter Standard Error 0.028	0.397 Liter Standard Error 0.028	—	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak FVC (0-3h) Response After 48 Weeks	0.137 Liter Standard Error 0.029	0.325 Liter Standard Error 0.028	0.352 Liter Standard Error 0.028	0.329 Liter Standard Error 0.028	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: FAS

Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline.

Outcome measures

Outcome measures
Measure	Placebo n=233 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=230 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=233 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=232 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Peak Expiratory Flow Rate (PEFR) at Week 24 morning PEFR (N=225, 227, 226, 224)	196.789 L/min Standard Error 3.270	210.496 L/min Standard Error 3.253	217.660 L/min Standard Error 3.274	211.038 L/min Standard Error 3.299	—	—	—	—
Peak Expiratory Flow Rate (PEFR) at Week 24 evening PEFR (N=224, 223, 227, 222)	202.505 L/min Standard Error 3.281	219.905 L/min Standard Error 3.289	225.380 L/min Standard Error 3.281	218.321 L/min Standard Error 3.321	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Population: FAS

Mean number of puffs of rescue medication used per day (daytime/nighttime/total)

Outcome measures

Outcome measures
Measure	Placebo n=227 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=228 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=229 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=224 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Use of Rescue Medication at Week 24 Daytime	1.189 Number of puffs Standard Error 0.089	1.036 Number of puffs Standard Error 0.089	0.923 Number of puffs Standard Error 0.089	0.967 Number of puffs Standard Error 0.090	—	—	—	—
Use of Rescue Medication at Week 24 Nighttime	1.713 Number of puffs Standard Error 0.112	1.435 Number of puffs Standard Error 0.111	1.348 Number of puffs Standard Error 0.112	1.393 Number of puffs Standard Error 0.113	—	—	—	—
Use of Rescue Medication at Week 24 Total	2.893 Number of puffs Standard Error 0.187	2.470 Number of puffs Standard Error 0.187	2.277 Number of puffs Standard Error 0.188	2.353 Number of puffs Standard Error 0.190	—	—	—	—

SECONDARY outcome

Timeframe: Week 6

Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=225 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=225 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=221 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Patient's Global Rating (PGR) at 6 Weeks	3.4 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	3.2 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 12

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=225 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=225 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=221 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Patient's Global Rating (PGR) at 12 Weeks	3.3 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 24

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=225 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=225 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=221 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Patient's Global Rating (PGR) at 24 Weeks	3.3 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	3.1 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Placebo n=224 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=225 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=225 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=221 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Patient's Global Rating (PGR) at 48 Weeks	3.2 score on a scale Standard Error 0.1	3.2 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	3.2 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 6 Weeks	0.980 score on a scale Standard Error 0.221	1.417 score on a scale Standard Error 0.221	1.686 score on a scale Standard Error 0.222	1.444 score on a scale Standard Error 0.224	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 12 Weeks	1.080 score on a scale Standard Error 0.224	1.742 score on a scale Standard Error 0.222	1.747 score on a scale Standard Error 0.224	1.499 score on a scale Standard Error 0.226	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 18

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 18 Weeks	1.0454 score on a scale Standard Error 0.227	1.470 score on a scale Standard Error 0.223	1.537 score on a scale Standard Error 0.224	1.579 score on a scale Standard Error 0.227	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 32

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 32 Weeks	1.168 score on a scale Standard Error 0.232	1.658 score on a scale Standard Error 0.228	1.522 score on a scale Standard Error 0.228	1.477 score on a scale Standard Error 0.229	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 40

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 40 Weeks	1.064 score on a scale Standard Error 0.234	1.377 score on a scale Standard Error 0.229	1.545 score on a scale Standard Error 0.229	1.178 score on a scale Standard Error 0.231	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48

Outcome measures

Outcome measures
Measure	Placebo n=221 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=221 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=220 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=215 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Mahler Transitional Dyspnea Index Focal Score at 48 Weeks	1.113 score on a scale Standard Error 0.234	1.510 score on a scale Standard Error 0.231	1.831 score on a scale Standard Error 0.230	1.280 score on a scale Standard Error 0.232	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=174 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=173 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=175 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) n=58 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) n=175 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	173 Days Interval 74.0 to 298.0	177 Days Interval 118.0 to 221.0	252 Days Interval 164.0 to N/A indicates this statistic was not available due to the low number of events observed.	270 Days Interval 180.0 to N/A indicates this statistic was not available due to the low number of events observed.	252 Days Interval 92.0 to N/A indicates this statistic was not available due to the low number of events observed.	234 Days Interval 184.0 to 326.0	149 Days Interval 106.0 to 217.0	232 Days Interval 161.0 to 368.0

SECONDARY outcome

Timeframe: Baseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=174 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=173 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=175 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) n=58 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) n=175 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	NA Days N/A indicates this statistic was not available due to the low number of events observed.	368.0 Days N/A indicates this statistic was not available due to the low number of events observed.

SECONDARY outcome

Timeframe: Baseline to end of study at 48 weeks.

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.

Outcome measures

Outcome measures
Measure	Placebo n=61 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=174 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=173 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) n=59 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=175 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) n=58 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) n=175 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation	176 Days Interval 75.0 to N/A indicates this statistic was not available due to the low number of events observed.	214 Days Interval 144.0 to N/A indicates this statistic was not available due to the low number of events observed.	264 Days Interval 164.0 to N/A indicates this statistic was not available due to the low number of events observed.	312 Days Interval 205.0 to N/A indicates this statistic was not available due to the low number of events observed.	324 Days Interval 126.0 to N/A indicates this statistic was not available due to the low number of events observed.	327 Days Interval 237.0 to N/A indicates this statistic was not available due to the low number of events observed.	190 Days Interval 112.0 to 260.0	325 Days Interval 181.0 to N/A indicates this statistic was not available due to the low number of events observed.

SECONDARY outcome

Timeframe: Baseline to end of study at week 48 visit

Population: Treated set- all patients who received at least one dose of study medication

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria.

Outcome measures

Outcome measures
Measure	Placebo n=235 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=232 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=234 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Number of COPD Exacerbations	0.6890 Number of COPD ex. per patient year Standard Error 0.0829	0.5409 Number of COPD ex. per patient year Standard Error 0.0690	0.5947 Number of COPD ex. per patient year Standard Error 0.0736	0.7325 Number of COPD ex. per patient year Standard Error 0.0861	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to end of study at week 48 visit

Population: Treated set- all patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Placebo n=235 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=232 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=234 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Number of COPD Exacerbations Requiring Hospitalization	0.0986 Number of COPD ex. per patient year Standard Error 0.0258	0.0781 Number of COPD ex. per patient year Standard Error 0.0221	0.0993 Number of COPD ex. per patient year Standard Error 0.0253	0.1025 Number of COPD ex. per patient year Standard Error 0.0262	—	—	—	—

SECONDARY outcome

Timeframe: Baseline to end of study at 48 weeks.

Population: Treated set- all patients who received at least one dose of study medication

Outcome measures

Outcome measures
Measure	Placebo n=235 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=232 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=234 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations	0.5548 Number of COPD ex. per patient year Standard Error 0.0719	0.4128 Number of COPD ex. per patient year Standard Error 0.0578	0.4351 Number of COPD ex. per patient year Standard Error 0.0601	0.5415 Number of COPD ex. per patient year Standard Error 0.0699	—	—	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Treated set.

Occurence of cardiac disorders and investigations related to treatment.

Outcome measures

Outcome measures
Measure	Placebo n=235 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=232 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=234 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Changes in Safety Parameters Related to Treatment Blood creatine phosphokinase increased	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.4 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Atrial fibrillation	0.9 percentage of participants	0.0 percentage of participants	0.9 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Sinus tachycardia	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.9 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Acute coronary syndrome	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Acute myocardial infarction	0.0 percentage of participants	0.0 percentage of participants	0.4 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Angina unstable	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Myocardial infarction	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Ventricular extrasystoles	0.4 percentage of participants	0.4 percentage of participants	0.0 percentage of participants	0.4 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Alanine aminotransferase increased	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Aspartate aminotransferase increased	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.4 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Electrocardiogram ST segment depression	0.0 percentage of participants	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Electrocardiogram T wave inversion	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—
Changes in Safety Parameters Related to Treatment Gamma-glutamyltransferase increased	0.4 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—	—

SECONDARY outcome

Timeframe: within 2 hours before first study drug administration and 10 minutes post-dose at week 6, 12 and 18

Population: Pharmacokinetic set includes all patients in the treated set who had at least one valid olodaterol plasma concentration measurement after initial administration of study drug. This set is restricted to patients in either the Olodaterol 5 μg or 10 μg dose group.

Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.

Outcome measures

Outcome measures
Measure	Placebo Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=182 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=216 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Olo 10 mcg qd (Tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Form 12 mcg (Tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Form 12 mcg (Non-tiotropium) Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Absolute Plasma Concentrations	—	3.920 pg/mL Geometric Coefficient of Variation 50.510	6.977 pg/mL Geometric Coefficient of Variation 68.643	—	—	—	—	—

Adverse Events

Placebo

Serious events: 48 serious events

Other events: 100 other events

Deaths: 0 deaths

Olodaterol (Olo) 5 mcg qd

Serious events: 34 serious events

Other events: 103 other events

Deaths: 0 deaths

Olodaterol (Olo) 10 mcg qd

Serious events: 41 serious events

Other events: 101 other events

Deaths: 0 deaths

Form 12 mcg

Serious events: 36 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=235 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=232 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=234 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 participants at risk Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Cardiac disorders Acute coronary syndrome	0.85% 2/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Acute left ventricular failure	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Acute myocardial infarction	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	1.3% 3/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Angina pectoris	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Angina unstable	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Arrhythmia	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Cardiac disorders Atrial fibrillation	0.85% 2/235 • 48 weeks	0.86% 2/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cardiac arrest	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Cardiac disorders Cardiac failure	0.00% 0/235 • 48 weeks	0.86% 2/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cardiac failure acute	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cardiac failure congestive	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cardio-respiratory arrest	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cardiopulmonary failure	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Cor pulmonale	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Coronary artery disease	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Myocardial infarction	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Cardiac disorders Myocardial ischaemia	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Right ventricular failure	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Tachycardia	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Cardiac disorders Ventricular extrasystoles	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Ear and labyrinth disorders Vertigo	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Eye disorders Amaurosis fugax	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Gastrointestinal disorders Abdominal pain	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.43% 1/233 • 48 weeks
Gastrointestinal disorders Gastric polyps	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Gastrointestinal disorders Ileus	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Gastrointestinal disorders Nausea	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Gastrointestinal disorders Volvulus	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Gastrointestinal disorders Vomiting	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
General disorders Asthenia	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Chest pain	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Chills	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Death	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.43% 1/233 • 48 weeks
General disorders Influenza like illness	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Multi-organ failure	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
General disorders Oedema peripheral	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Pain	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
General disorders Pyrexia	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
General disorders Sudden cardiac death	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Hepatobiliary disorders Acute hepatic failure	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Hepatobiliary disorders Cholecystitis acute	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Immune system disorders Anaphylactic shock	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Infections and infestations Bronchitis	0.85% 2/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Carbuncle	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Cellulitis pharyngeal	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Cholecystitis infective	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Cystitis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Incision site infection	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Infections and infestations Kidney infection	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Lobar pneumonia	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Infections and infestations Lower respiratory tract infection	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Nasopharyngitis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Peritonsillar abscess	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Pneumonia	0.85% 2/235 • 48 weeks	1.3% 3/232 • 48 weeks	3.0% 7/234 • 48 weeks	1.7% 4/233 • 48 weeks
Infections and infestations Pulmonary tuberculosis	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Pyelonephritis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Respiratory tract infection	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Sepsis	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Infections and infestations Tuberculosis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Upper respiratory tract infection	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Infections and infestations Viral infection	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Arthropod sting	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Injury, poisoning and procedural complications Femur fracture	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Fibula fracture	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Foot fracture	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Laceration	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Patella fracture	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Post procedural haematuria	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Injury, poisoning and procedural complications Rib fracture	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Injury, poisoning and procedural complications Road traffic accident	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Injury, poisoning and procedural complications Tendon rupture	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Metabolism and nutrition disorders Malnutrition	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.85% 2/234 • 48 weeks	0.00% 0/233 • 48 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.86% 2/233 • 48 weeks
Musculoskeletal and connective tissue disorders Meniscal degeneration	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenoma benign	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal cancer	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.43% 1/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to lung	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer recurrent	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Cerebral ischaemia	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Cerebrovascular accident	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Dizziness	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Hypoxic-ischaemic encephalopathy	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Ischaemic stroke	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Syncope	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Transient ischaemic attack	0.85% 2/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Nervous system disorders Tremor	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Psychiatric disorders Depression	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Psychiatric disorders Psychotic disorder	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Renal and urinary disorders Hydronephrosis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Renal and urinary disorders Renal failure acute	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Reproductive system and breast disorders Prostatitis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Bronchiectasis	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	7.7% 18/235 • 48 weeks	6.0% 14/232 • 48 weeks	7.3% 17/234 • 48 weeks	7.7% 18/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.43% 1/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.86% 2/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Hypoxia	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Mediastinal mass	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.43% 1/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	1.3% 3/234 • 48 weeks	0.43% 1/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.3% 3/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Surgical and medical procedures Cholecystectomy	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Surgical and medical procedures Mastoidectomy	0.00% 0/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Vascular disorders Arteriosclerosis obliterans	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Vascular disorders Deep vein thrombosis	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.43% 1/234 • 48 weeks	0.00% 0/233 • 48 weeks
Vascular disorders Hypertensive crisis	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Vascular disorders Hypertensive emergency	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Vascular disorders Hypovolaemic shock	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.43% 1/233 • 48 weeks
Vascular disorders Venous occlusion	0.43% 1/235 • 48 weeks	0.00% 0/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks
Vascular disorders Venous thrombosis	0.00% 0/235 • 48 weeks	0.43% 1/232 • 48 weeks	0.00% 0/234 • 48 weeks	0.00% 0/233 • 48 weeks

Other adverse events

Other adverse events
Measure	Placebo n=235 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olodaterol (Olo) 5 mcg qd n=232 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol (Olo) 10 mcg qd n=234 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=233 participants at risk Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
General disorders Pyrexia	3.0% 7/235 • 48 weeks	2.6% 6/232 • 48 weeks	5.1% 12/234 • 48 weeks	3.9% 9/233 • 48 weeks
Infections and infestations Bronchitis	3.0% 7/235 • 48 weeks	5.6% 13/232 • 48 weeks	4.3% 10/234 • 48 weeks	3.4% 8/233 • 48 weeks
Infections and infestations Nasopharyngitis	9.4% 22/235 • 48 weeks	15.5% 36/232 • 48 weeks	12.0% 28/234 • 48 weeks	9.9% 23/233 • 48 weeks
Infections and infestations Upper respiratory tract infection	7.7% 18/235 • 48 weeks	6.0% 14/232 • 48 weeks	6.4% 15/234 • 48 weeks	9.0% 21/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	21.7% 51/235 • 48 weeks	17.2% 40/232 • 48 weeks	20.5% 48/234 • 48 weeks	21.9% 51/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Cough	6.8% 16/235 • 48 weeks	2.6% 6/232 • 48 weeks	5.1% 12/234 • 48 weeks	6.0% 14/233 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.3% 10/235 • 48 weeks	4.3% 10/232 • 48 weeks	1.3% 3/234 • 48 weeks	7.3% 17/233 • 48 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication
Publication restrictions are in place

Restriction type: OTHER