Trial Outcomes & Findings for Safety and Efficacy of BI 1744 CL in Patients With Chronic Obstructive Pulmonary Disease I (NCT NCT00793624)

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

906 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

Two subjects were randomized but not treated due to withdrawn consent and inability to perform spirometry prior to dosing.

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	225	227	225	227
Overall Study COMPLETED	168	191	186	184
Overall Study NOT COMPLETED	57	36	39	43

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	18	16	15	20
Overall Study Lost to Follow-up	2	2	4	0
Overall Study Withdrawal by Subject	20	9	11	14
Overall Study Lack of Efficacy	9	2	1	3
Overall Study Non compliance with protocol	2	3	2	3
Overall Study Other reason not described above	6	4	6	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=225 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=227 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=227 Participants Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Total n=904 Participants Total of all reporting groups
Age, Continuous	64.0 years STANDARD_DEVIATION 8.4 • n=5 Participants	63.7 years STANDARD_DEVIATION 9.1 • n=7 Participants	62.6 years STANDARD_DEVIATION 8.8 • n=5 Participants	64.8 years STANDARD_DEVIATION 8.6 • n=4 Participants	63.8 years STANDARD_DEVIATION 8.7 • n=21 Participants
Sex: Female, Male Female	45 Participants n=5 Participants	50 Participants n=7 Participants	55 Participants n=5 Participants	48 Participants n=4 Participants	198 Participants n=21 Participants
Sex: Female, Male Male	180 Participants n=5 Participants	177 Participants n=7 Participants	170 Participants n=5 Participants	179 Participants n=4 Participants	706 Participants n=21 Participants
Tiotropium (Tio) Use Stratum Non-tiotropium	169 Number of participants n=5 Participants	168 Number of participants n=7 Participants	167 Number of participants n=5 Participants	169 Number of participants n=4 Participants	673 Number of participants n=21 Participants
Tiotropium (Tio) Use Stratum Tiotropium	56 Number of participants n=5 Participants	59 Number of participants n=7 Participants	58 Number of participants n=5 Participants	58 Number of participants n=4 Participants	231 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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	-0.009 Liter Standard Error 0.016	0.142 Liter Standard Error 0.015	0.156 Liter Standard Error 0.015	0.168 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 24	-0.056 Liter Standard Error 0.015	0.021 Liter Standard Error 0.015	0.028 Liter Standard Error 0.015	-0.002 Liter Standard Error 0.015	—	—	—	—

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=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	2.046 score on a scale Standard Error 0.255	2.234 score on a scale Standard Error 0.240	2.068 score on a scale Standard Error 0.245	1.818 score on a scale Standard Error 0.247	—	—	—	—

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=185 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=200 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=202 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	41.068 score on a scale Standard Error 1.038	38.627 score on a scale Standard Error 0.995	37.674 score on a scale Standard Error 0.998	40.116 score on a scale Standard Error 0.994	—	—	—	—

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=185 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=200 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=202 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	42.105 score on a scale Standard Error 1.027	39.320 score on a scale Standard Error 0.986	36.961 score on a scale Standard Error 0.989	40.351 score on a scale Standard Error 0.992	—	—	—	—

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=185 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=200 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=202 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	40.415 score on a scale Standard Error 1.057	38.545 score on a scale Standard Error 1.000	36.850 score on a scale Standard Error 1.015	40.431 score on a scale Standard Error 1.015	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.015 Liter Standard Error 0.015	0.201 Liter Standard Error 0.015	0.181 Liter Standard Error 0.015	0.221 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 6

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.001 Liter Standard Error 0.015	0.178 Liter Standard Error 0.015	0.161 Liter Standard Error 0.015	0.194 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 12

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	-0.003 Liter Standard Error 0.015	0.176 Liter Standard Error 0.015	0.167 Liter Standard Error 0.015	0.182 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 48

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	-0.023 Liter Standard Error 0.016	0.122 Liter Standard Error 0.015	0.123 Liter Standard Error 0.015	0.149 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 2	-0.019 Liter Standard Error 0.015	0.068 Liter Standard Error 0.014	0.060 Liter Standard Error 0.014	0.061 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 6.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 6	-0.037 Liter Standard Error 0.015	0.049 Liter Standard Error 0.014	0.041 Liter Standard Error 0.014	0.042 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 12.

Population: FAS

Outcome measures

Outcome measures
Measure	Placebo n=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 12	-0.027 Liter Standard Error 0.015	0.056 Liter Standard Error 0.014	0.048 Liter Standard Error 0.014	0.033 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 18	-0.019 Liter Standard Error 0.015	0.046 Liter Standard Error 0.014	0.026 Liter Standard Error 0.015	0.023 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 32	-0.023 Liter Standard Error 0.015	0.023 Liter Standard Error 0.015	0.026 Liter Standard Error 0.015	0.021 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 40	-0.020 Liter Standard Error 0.016	0.020 Liter Standard Error 0.015	0.017 Liter Standard Error 0.015	0.004 Liter Standard Error 0.015	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FEV1 Response at Week 48	-0.065 Liter Standard Error 0.015	0.003 Liter Standard Error 0.015	-0.009 Liter Standard Error 0.015	-0.006 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 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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.100 Liter Standard Error 0.016	0.277 Liter Standard Error 0.016	0.250 Liter Standard Error 0.016	0.290 Liter Standard Error 0.016	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.081 Liter Standard Error 0.016	0.248 Liter Standard Error 0.016	0.234 Liter Standard Error 0.016	0.264 Liter Standard Error 0.016	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.082 Liter Standard Error 0.016	0.247 Liter Standard Error 0.016	0.241 Liter Standard Error 0.016	0.256 Liter Standard Error 0.016	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.068 Liter Standard Error 0.017	0.216 Liter Standard Error 0.016	0.225 Liter Standard Error 0.016	0.236 Liter Standard Error 0.016	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.053 Liter Standard Error 0.017	0.192 Liter Standard Error 0.016	0.193 Liter Standard Error 0.016	0.215 Liter Standard Error 0.016	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.076 Liter Standard Error 0.028	0.299 Liter Standard Error 0.027	0.311 Liter Standard Error 0.027	0.383 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 on Week 6

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.016 Liter Standard Error 0.028	0.252 Liter Standard Error 0.027	0.265 Liter Standard Error 0.027	0.326 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 on Week 12

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.023 Liter Standard Error 0.028	0.233 Liter Standard Error 0.027	0.278 Liter Standard Error 0.027	0.300 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 on Week 24

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.037 Liter Standard Error 0.029	0.220 Liter Standard Error 0.027	0.252 Liter Standard Error 0.028	0.279 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 on Week 48

Outcome measures

Outcome measures
Measure	Placebo n=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.016 Liter Standard Error 0.029	0.196 Liter Standard Error 0.028	0.219 Liter Standard Error 0.028	0.260 Liter Standard Error 0.028	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 2	0.042 Liter Standard Error 0.028	0.110 Liter Standard Error 0.027	0.119 Liter Standard Error 0.028	0.126 Liter Standard Error 0.028	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 6	-0.046 Liter Standard Error 0.029	0.065 Liter Standard Error 0.027	0.085 Liter Standard Error 0.028	0.090 Liter Standard Error 0.028	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 12	-0.018 Liter Standard Error 0.029	0.079 Liter Standard Error 0.028	0.087 Liter Standard Error 0.028	0.068 Liter Standard Error 0.028	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 18	0.060 Liter Standard Error 0.029	0.066 Liter Standard Error 0.028	0.078 Liter Standard Error 0.028	0.063 Liter Standard Error 0.028	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 24	-0.018 Liter Standard Error 0.029	0.038 Liter Standard Error 0.028	0.064 Liter Standard Error 0.028	0.001 Liter Standard Error 0.029	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 32	0.019 Liter Standard Error 0.030	0.080 Liter Standard Error 0.028	0.084 Liter Standard Error 0.028	0.077 Liter Standard Error 0.029	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 48	-0.061 Liter Standard Error 0.030	0.022 Liter Standard Error 0.028	-0.002 Liter Standard Error 0.029	0.006 Liter Standard Error 0.029	—	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=220 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=219 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
Trough FVC Response at Week 40	0.028 Liter Standard Error 0.030	0.087 Liter Standard Error 0.028	0.086 Liter Standard Error 0.028	0.052 Liter Standard Error 0.029	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.268 Liter Standard Error 0.029	0.454 Liter Standard Error 0.028	0.474 Liter Standard Error 0.028	0.551 Liter Standard Error 0.029	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.202 Liter Standard Error 0.029	0.411 Liter Standard Error 0.028	0.433 Liter Standard Error 0.029	0.467 Liter Standard Error 0.029	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.194 Liter Standard Error 0.030	0.382 Liter Standard Error 0.029	0.432 Liter Standard Error 0.029	0.450 Liter Standard Error 0.029	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.207 Liter Standard Error 0.030	0.379 Liter Standard Error 0.029	0.414 Liter Standard Error 0.029	0.424 Liter Standard Error 0.029	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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	0.193 Liter Standard Error 0.031	0.344 Liter Standard Error 0.029	0.371 Liter Standard Error 0.030	0.416 Liter Standard Error 0.030	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=222 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=223 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=223 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=214, 212, 216, 218)	196.429 L/min Standard Error 3.392	211.496 L/min Standard Error 3.420	211.428 L/min Standard Error 3.379	214.070 L/min Standard Error 3.373	—	—	—	—
Peak Expiratory Flow Rate (PEFR) at Week 24 evening PEFR (N=215, 211, 215, 221)	202.256 L/min Standard Error 3.363	219.977 L/min Standard Error 3.408	220.727 L/min Standard Error 3.360	220.129 L/min Standard Error 3.332	—	—	—	—

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=217 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 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 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
Use of Rescue Medication at Week 24 Daytime	1.364 Number of puffs Standard Error 0.097	0.961 Number of puffs Standard Error 0.099	1.037 Number of puffs Standard Error 0.097	1.217 Number of puffs Standard Error 0.097	—	—	—	—
Use of Rescue Medication at Week 24 Nighttime	2.051 Number of puffs Standard Error 0.125	1.449 Number of puffs Standard Error 0.126	1.471 Number of puffs Standard Error 0.125	1.701 Number of puffs Standard Error 0.124	—	—	—	—
Use of Rescue Medication at Week 24 Total	3.390 Number of puffs Standard Error 0.196	2.399 Number of puffs Standard Error 0.198	2.488 Number of puffs Standard Error 0.196	2.917 Number of puffs Standard Error 0.195	—	—	—	—

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=194 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
Patient's Global Rating (PGR) at 6 Weeks	3.4 score on a scale Standard Error 0.1	3.0 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 12

Outcome measures

Outcome measures
Measure	Placebo n=194 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
Patient's Global Rating (PGR) at 12 Weeks	3.3 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	2.9 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=194 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
Patient's Global Rating (PGR) at 24 Weeks	3.1 score on a scale Standard Error 0.1	2.9 score on a scale Standard Error 0.1	2.9 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Week 48

Outcome measures

Outcome measures
Measure	Placebo n=194 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
Patient's Global Rating (PGR) at 48 Weeks	3.1 score on a scale Standard Error 0.1	3.0 score on a scale Standard Error 0.1	2.9 score on a scale Standard Error 0.1	2.9 score on a scale Standard Error 0.1	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 6

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	0.995 score on a scale Standard Error 0.248	1.566 score on a scale Standard Error 0.236	1.660 score on a scale Standard Error 0.240	1.753 score on a scale Standard Error 0.243	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 12

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	1.412 score on a scale Standard Error 0.252	1.792 score on a scale Standard Error 0.239	1.955 score on a scale Standard Error 0.242	1.805 score on a scale Standard Error 0.245	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 18

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	1.665 score on a scale Standard Error 0.254	1.897 score on a scale Standard Error 0.240	2.099 score on a scale Standard Error 0.244	1.689 score on a scale Standard Error 0.246	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 32

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	1.732 score on a scale Standard Error 0.257	1.898 score on a scale Standard Error 0.241	1.698 score on a scale Standard Error 0.247	1.966 score on a scale Standard Error 0.249	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 40

Outcome measures

Outcome measures
Measure	Placebo n=192 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=212 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=207 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Form 12 mcg n=202 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	1.952 score on a scale Standard Error 0.259	1.839 score on a scale Standard Error 0.241	1.887 score on a scale Standard Error 0.249	1.575 score on a scale Standard Error 0.251	—	—	—	—

SECONDARY outcome

Timeframe: Baseline, Week 48