Trial Outcomes & Findings for 12 / 48 Week Pivotal PFT vs PBO in COPD I (NCT NCT00782210)

NCT ID: NCT00782210

Last Updated: 2014-06-09

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: 625 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 Day 85
• Results posted on: 2014-06-09

Participant Flow

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.
Overall Study STARTED	209	208	207
Overall Study COMPLETED	159	173	172
Overall Study NOT COMPLETED	50	35	35

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.
Overall Study Adverse Event	21	17	16
Overall Study Lost to Follow-up	2	1	2
Overall Study Withdrawal by Subject	11	8	11
Overall Study Non compliance with protocol	0	3	2
Overall Study Lack of Efficacy	13	4	1
Overall Study Other reason not described above	3	2	3

Baseline Characteristics

12 / 48 Week Pivotal PFT vs PBO in COPD I

Baseline characteristics by cohort

Measure	Placebo n=209 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=208 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.	Total n=624 Participants Total of all reporting groups
Age, Continuous	65.8 years STANDARD_DEVIATION 8.5 • n=5 Participants	64.0 years STANDARD_DEVIATION 8.6 • n=7 Participants	65.0 years STANDARD_DEVIATION 8.2 • n=5 Participants	64.9 years STANDARD_DEVIATION 8.5 • n=4 Participants
Sex: Female, Male Female	57 Participants n=5 Participants	58 Participants n=7 Participants	52 Participants n=5 Participants	167 Participants n=4 Participants
Sex: Female, Male Male	152 Participants n=5 Participants	150 Participants n=7 Participants	155 Participants n=5 Participants	457 Participants n=4 Participants
Tiotropium (Tio) Use Stratum Non-tiotropium	160 Number of participants n=5 Participants	161 Number of participants n=7 Participants	156 Number of participants n=5 Participants	477 Number of participants n=4 Participants
Tiotropium (Tio) Use Stratum Tiotropium	49 Number of participants n=5 Participants	47 Number of participants n=7 Participants	51 Number of participants n=5 Participants	147 Number of participants n=4 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 Day 85

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 Day 85 (12 weeks) for either co-primary efficacy variable.

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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)	-0.007 Liter Standard Error 0.014	0.165 Liter Standard Error 0.014	0.169 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 and - 10 mins prior to study drug at Day 85.

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response at Day 85 (12 Weeks)	-0.041 Liter Standard Error 0.014	0.050 Liter Standard Error 0.014	0.060 Liter Standard Error 0.014	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

Population: Patients in FAS with spirometry data after 3 hours at Visit 5 (12-hour pulmonary function test set)

Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=71 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=85 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=85 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	-0.029 Liter Standard Error 0.025	0.144 Liter Standard Error 0.022	0.139 Liter Standard Error 0.022	—	—	—

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 at day 1

Population: FAS

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 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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 1	0.024 Liter Standard Error 0.014	0.189 Liter Standard Error 0.014	0.199 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

Population: FAS

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 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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks	-0.000 Liter Standard Error 0.014	0.180 Liter Standard Error 0.014	0.192 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 -1h, -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Population: FAS

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 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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks	-0.001 Liter Standard Error 0.014	0.169 Liter Standard Error 0.014	0.165 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

Population: FAS

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 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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks	-0.18 Liter Standard Error 0.014	0.156 Liter Standard Error 0.014	0.143 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 48 weeks

Population: FAS

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 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.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks	-0.043 Liter Standard Error 0.014	0.130 Liter Standard Error 0.014	0.126 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 after 2 weeks

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 a -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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 2 Weeks	-0.019 Liter Standard Error 0.014	0.076 Liter Standard Error 0.014	0.091 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 after 6 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 6 Weeks	-0.022 Liter Standard Error 0.014	0.073 Liter Standard Error 0.014	0.069 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 after 18 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 18 Weeks	-0.042 Liter Standard Error 0.014	0.056 Liter Standard Error 0.014	0.059 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 after 24 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 24 Weeks	-0.050 Liter Standard Error 0.014	0.036 Liter Standard Error 0.014	0.039 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 after 32 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 32 Weeks	-0.051 Liter Standard Error 0.014	0.041 Liter Standard Error 0.014	0.034 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 after 40 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 40 Weeks	-0.061 Liter Standard Error 0.014	0.046 Liter Standard Error 0.014	0.044 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 after 48 weeks

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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FEV1 Response After 48 Weeks	-0.74 Liter Standard Error 0.014	0.019 Liter Standard Error 0.014	0.017 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 at Day 1

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response At Day 1	0.104 Liter Standard Error 0.015	0.259 Liter Standard Error 0.015	0.275 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

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response After 2 Weeks	0.077 Liter Standard Error 0.015	0.254 Liter Standard Error 0.015	0.267 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 6 weeks

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response After 6 Weeks	0.066 Liter Standard Error 0.015	0.238 Liter Standard Error 0.015	0.238 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 12 weeks

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response After 12 Weeks	0.071 Liter Standard Error 0.015	0.235 Liter Standard Error 0.015	0.236 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 24 weeks

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response After 24 Weeks	0.055 Liter Standard Error 0.016	0.230 Liter Standard Error 0.015	0.206 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

Population: FAS

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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Peak FEV1 (0-3h) Response After 48 Weeks	0.029 Liter Standard Error 0.016	0.198 Liter Standard Error 0.016	0.192 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 at Day 1

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1	0.063 Liter Standard Error 0.027	0.350 Liter Standard Error 0.027	0.392 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

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks	0.026 Liter Standard Error 0.027	0.323 Liter Standard Error 0.027	0.353 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

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks	0.022 Liter Standard Error 0.028	0.276 Liter Standard Error 0.028	0.316 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

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks	0.003 Liter Standard Error 0.028	0.277 Liter Standard Error 0.028	0.295 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

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks	0.026 Liter Standard Error 0.028	0.261 Liter Standard Error 0.028	0.281 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

Population: FAS

Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a 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. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.

Outcome measures

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks	-0.040 Liter Standard Error 0.028	0.204 Liter Standard Error 0.028	0.231 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 after 2 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 2 Weeks	-0.015 Liter Standard Error 0.027	0.132 Liter Standard Error 0.027	0.169 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 after 6 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 6 Weeks	-0.005 Liter Standard Error 0.027	0.125 Liter Standard Error 0.027	0.135 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 after 12 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 12 Weeks	-0.030 Liter Standard Error 0.027	0.085 Liter Standard Error 0.027	0.130 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 after 18 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 18 Weeks	-0.028 Liter Standard Error 0.028	0.102 Liter Standard Error 0.027	0.134 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 after 24 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 24 Weeks	-0.028 Liter Standard Error 0.028	0.055 Liter Standard Error 0.027	0.096 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 after 32 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 32 Weeks	-0.026 Liter Standard Error 0.028	0.065 Liter Standard Error 0.028	0.097 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 after 40 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 40 Weeks	-0.044 Liter Standard Error 0.028	0.087 Liter Standard Error 0.028	0.111 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 after 48 weeks

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 FVCs obtained 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

Measure	Placebo n=200 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Trough FVC Response After 48 Weeks	-0.083 Liter Standard Error 0.028	0.011 Liter Standard Error 0.028	0.032 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 at Day 1

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response At Day 1	0.245 Liter Standard Error 0.029	0.509 Liter Standard Error 0.029	0.546 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

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response After 2 Weeks	0.207 Liter Standard Error 0.029	0.471 Liter Standard Error 0.029	0.499 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

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response After 6 Weeks	0.180 Liter Standard Error 0.029	0.430 Liter Standard Error 0.029	0.460 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

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response After 12 Weeks	0.169 Liter Standard Error 0.029	0.421 Liter Standard Error 0.029	0.430 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

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response After 24 Weeks	0.188 Liter Standard Error 0.030	0.419 Liter Standard Error 0.029	0.420 Liter Standard Error 0.030	—	—	—

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

Population: FAS

Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (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

Measure	Placebo n=208 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=206 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=206 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
FVC Peak (0-3h) Response After 48 Weeks	0.109 Liter Standard Error 0.030	0.356 Liter Standard Error 0.030	0.369 Liter Standard Error 0.030	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)

Population: Patients in FAS with spirometry data after 3 hours at Visit 5 (12-hour pulmonary function test set)

Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.

Outcome measures

Measure	Placebo n=71 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=85 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=85 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	-0.019 Liter Standard Error 0.049	0.283 Liter Standard Error 0.045	0.230 Liter Standard Error 0.044	—	—	—

SECONDARY outcome

Timeframe: immediately upon arising (before drug administration) from Screening to week 48

Population: FAS

Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.

Outcome measures

Measure	Placebo n=204 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=202 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=203 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	180.019 L/min Standard Error 3.182	193.376 L/min Standard Error 3.207	195.475 L/min Standard Error 3.184	—	—	—

SECONDARY outcome

Timeframe: at bedtime from Screening to week 48

Population: FAS

Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.

Outcome measures

Measure	Placebo n=203 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=199 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=203 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	190.676 L/min Standard Error 3.165	207.862 L/min Standard Error 3.202	205.236 L/min Standard Error 3.166	—	—	—

SECONDARY outcome

Timeframe: From Screening to week 48

Population: FAS

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.

Outcome measures

Measure	Placebo n=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=204 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=204 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Weekly Mean Daytime Rescue Use	1.487 Number of puffs Standard Error 0.136	0.967 Number of puffs Standard Error 0.137	0.839 Number of puffs Standard Error 0.136	—	—	—

SECONDARY outcome

Timeframe: From Screening to week 48

Population: FAS

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.

Outcome measures

Measure	Placebo n=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=204 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=204 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Weekly Mean Nighttime Rescue Use	2.283 Number of puffs Standard Error 0.151	1.701 Number of puffs Standard Error 0.152	1.492 Number of puffs Standard Error 0.152	—	—	—

SECONDARY outcome

Timeframe: From Screening to week 48

Population: FAS

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night.

Outcome measures

Measure	Placebo n=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=204 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=204 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Weekly Mean Daily (24h) Rescue Use	3.747 Number of puffs Standard Error 0.265	2.642 Number of puffs Standard Error 0.267	2.312 Number of puffs Standard Error 0.265	—	—	—

SECONDARY outcome

Timeframe: Week 6 visit

Population: FAS

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.

Outcome measures

Measure	Placebo n=189 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=194 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=197 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Patient's Global Rating at Week 6	3.5 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	—	—	—

SECONDARY outcome

Timeframe: Week 12 visit

Population: FAS

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.

Outcome measures

Measure	Placebo n=189 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=194 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=197 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Patient's Global Rating at Week 12	3.4 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	—	—	—

SECONDARY outcome

Timeframe: Week 24 visit

Population: FAS

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.

Outcome measures

Measure	Placebo n=189 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=194 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=197 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Patient's Global Rating at Week 24	3.5 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	—	—	—

SECONDARY outcome

Timeframe: Week 48 visit

Population: FAS

Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.

Outcome measures

Measure	Placebo n=189 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=194 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=197 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Patient's Global Rating at Week 48	3.4 Point on scale Standard Error 0.1	3.1 Point on scale Standard Error 0.1	3.1 Point on scale Standard Error 0.1	—	—	—

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

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.

Outcome measures

Measure	Placebo n=49 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=160 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=47 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=161 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=51 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=156 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	194.0 days Interval 29.0 to 305.0	160.0 days Interval 139.0 to 204.0	203.0 days Interval 76.0 to N/A indicates this statistic was not available due to the low number of events observed.	236.0 days Interval 158.0 to 337.0	167.0 days Interval 74.0 to N/A indicates this statistic was not available due to the low number of events observed.	239.0 days Interval 192.0 to 306.0

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

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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.

Outcome measures

Measure	Placebo n=49 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=160 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=47 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=161 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=51 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=156 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum
Time to First Chronic Obstructive Pulmonary Disease (COPD) 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 Interval 344.0 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 48 weeks.

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. 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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measure type is the First Quartile.

Outcome measures

Measure	Placebo n=49 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=160 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=47 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=161 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=51 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=156 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum
Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	194.0 days Interval 29.0 to 305.0	216.0 days Interval 158.0 to N/A indicates this statistic was not available due to the low number of events observed.	218.0 days Interval 76.0 to N/A indicates this statistic was not available due to the low number of events observed.	344.0 days Interval 206.0 to N/A indicates this statistic was not available due to the low number of events observed.	170.0 days Interval 74.0 to N/A indicates this statistic was not available due to the low number of events observed.	309.0 days Interval 220.0 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

Measure	Placebo n=209 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=208 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Number of COPD Exacerbations	0.7476 Number of COPD exacerbations Standard Error 0.0972	0.5842 Number of COPD exacerbations Standard Error 0.0791	0.6322 Number of COPD exacerbations Standard Error 0.0822	—	—	—

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. These exacerbations required hospitalization.

Outcome measures

Measure	Placebo n=209 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=208 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Number of COPD Exacerbations Requiring Hospitalization	0.1010 Number of COPD exacerbations Standard Error 0.0314	0.0662 Number of COPD exacerbations Standard Error 0.0224	0.1133 Number of COPD exacerbations Standard Error 0.0319	—	—	—

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.

Outcome measures

Measure	Placebo n=209 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=208 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	0.5745 Number of COPD exacerbations Standard Error 0.0844	0.4643 Number of COPD exacerbations Standard Error 0.0714	0.4875 Number of COPD exacerbations Standard Error 0.0723	—	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Treated set.

Occurrence of bronchoconstriction, cardiac disorders and investigations related to treatment. Bronchoconstriction is defined as any of the following events: Drop in trough FEV1 >= 15%, Rescue medication use within 30 min of inhaling randomized treatment on a clinic test day or Cough, wheeze, or dyspnoea AE within 30 min of inhaling randomized treatment on a clinic test day.

Outcome measures

Measure	Placebo n=209 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=208 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.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Changes in Safety Parameters Related to Treatment Bronchoconstriction	13.4 percentage of participants	2.4 percentage of participants	3.9 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Atrial fibrillation	0.0 percentage of participants	0.0 percentage of participants	1.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Angina pectoris	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Ventricular extrasystoles	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Electrocardiogram QT prolonged	0.5 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Forced expiratory volume decreased	0.0 percentage of participants	0.0 percentage of participants	0.5 percentage of participants	—	—	—

SECONDARY outcome

Timeframe: Day 1 and at 12, 24 and 48 weeks

Population: Treated set.

Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements.

Outcome measures

Measure	Placebo n=197 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=201 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=201 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	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
Change From Baseline in Potassium	0.0 mmol/L Standard Deviation 0.4	0.0 mmol/L Standard Deviation 0.3	0.0 mmol/L Standard Deviation 0.3	—	—	—

Adverse Events

Placebo

Serious events: 34 serious events

Other events: 93 other events

Deaths: 0 deaths

Olo 5 mcg

Serious events: 39 serious events

Other events: 83 other events

Deaths: 0 deaths

Olo 10 mcg

Serious events: 43 serious events

Other events: 78 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=209 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg n=208 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=207 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Vascular disorders Hypertensive crisis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Renal and urinary disorders Haematuria	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.48% 1/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Vascular disorders Aortic aneurysm	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Vascular disorders Deep vein thrombosis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Vascular disorders Femoral arterial stenosis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Renal and urinary disorders Renal failure acute	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	6.7% 14/209 • 48 weeks	4.8% 10/208 • 48 weeks	8.7% 18/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Acute coronary syndrome	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Cardiac disorders Acute myocardial infarction	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Angina pectoris	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Angina unstable	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Cardiac disorders Atrial fibrillation	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.97% 2/207 • 48 weeks
Cardiac disorders Atrioventricular block complete	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Cardiac failure	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Cardiac failure congestive	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Cardiomyopathy	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Cor pulmonale acute	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Cardiac disorders Coronary artery disease	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.48% 1/207 • 48 weeks
Cardiac disorders Coronary artery occlusion	0.96% 2/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Myocardial infarction	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Cardiac disorders Right ventricular failure	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Endocrine disorders Goitre	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Eye disorders Amaurosis fugax	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Abdominal pain	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Gastrointestinal disorders Colonic polyp	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Gastritis	0.96% 2/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Gastrointestinal disorders Gastrointestinal haemorrhage	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Ileus	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Inguinal hernia	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Gastrointestinal disorders Pancreatic mass	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
General disorders Chest pain	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
General disorders Non-cardiac chest pain	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
General disorders Oedema peripheral	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Hepatobiliary disorders Bile duct stone	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Infections and infestations Bone abscess	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Infections and infestations Cellulitis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Escherichia urinary tract infection	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.48% 1/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Lobar pneumonia	0.48% 1/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.48% 1/207 • 48 weeks
Infections and infestations Lung infection	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Orchitis	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Osteomyelitis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.48% 1/207 • 48 weeks
Infections and infestations Pneumonia	1.9% 4/209 • 48 weeks	0.96% 2/208 • 48 weeks	0.97% 2/207 • 48 weeks
Infections and infestations Pulmonary tuberculosis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Infections and infestations Urinary tract infection	0.00% 0/209 • 48 weeks	0.96% 2/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Arterial restenosis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Fall	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.97% 2/207 • 48 weeks
Injury, poisoning and procedural complications Fracture displacement	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Head injury	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Hip fracture	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Humerus fracture	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Neck injury	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Injury, poisoning and procedural complications Pneumothorax traumatic	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Injury, poisoning and procedural complications Skeletal injury	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Investigations Blood creatine phosphokinase increased	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Investigations Myoglobin blood increased	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.48% 1/207 • 48 weeks
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leukaemia	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.48% 1/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Sarcoma	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.97% 2/207 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Spinal cord neoplasm	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Nervous system disorders Basal ganglia haemorrhage	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Nervous system disorders Carotid artery stenosis	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.97% 2/207 • 48 weeks
Nervous system disorders Cervical myelopathy	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Nervous system disorders Epidural lipomatosis	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks
Nervous system disorders Hemiplegia	0.48% 1/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.00% 0/207 • 48 weeks
Nervous system disorders Presyncope	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Nervous system disorders Syncope	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.97% 2/207 • 48 weeks
Nervous system disorders Transient ischaemic attack	0.00% 0/209 • 48 weeks	0.48% 1/208 • 48 weeks	0.00% 0/207 • 48 weeks
Psychiatric disorders Bipolar disorder	0.00% 0/209 • 48 weeks	0.00% 0/208 • 48 weeks	0.48% 1/207 • 48 weeks

Other adverse events

Measure	Placebo n=209 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg n=208 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=207 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Infections and infestations Bronchitis	3.8% 8/209 • 48 weeks	5.3% 11/208 • 48 weeks	2.9% 6/207 • 48 weeks
Infections and infestations Nasopharyngitis	6.2% 13/209 • 48 weeks	10.1% 21/208 • 48 weeks	6.3% 13/207 • 48 weeks
Infections and infestations Upper respiratory tract infection	7.2% 15/209 • 48 weeks	10.1% 21/208 • 48 weeks	6.3% 13/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	27.3% 57/209 • 48 weeks	19.2% 40/208 • 48 weeks	23.7% 49/207 • 48 weeks
Respiratory, thoracic and mediastinal disorders Cough	3.8% 8/209 • 48 weeks	6.7% 14/208 • 48 weeks	3.4% 7/207 • 48 weeks
Vascular disorders Hypertension	5.7% 12/209 • 48 weeks	1.4% 3/208 • 48 weeks	3.9% 8/207 • 48 weeks

Additional Information

Boehringer Ingelheim Call Center

Boehringer Ingelheim Pharmaceuticals

Phone: 1-800-243-0127

Email: clintriage.rdg@boehringer-ingelheim.com

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