Trial Outcomes & Findings for 12 / 48 wk Pivotal PFT vs PBO in COPD II (NCT NCT00782509)

NCT ID: NCT00782509

Last Updated: 2014-06-27

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 644 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: 2014-06-27

Participant Flow

644 patients were randomised into the study, however two of the patients were not treated.

Participant milestones

Measure	Placebo Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Overall Study STARTED	216	209	217
Overall Study COMPLETED	175	185	181
Overall Study NOT COMPLETED	41	24	36

Reasons for withdrawal

Measure	Placebo Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Overall Study Adverse Event	20	10	20
Overall Study Lost to Follow-up	1	2	3
Overall Study Withdrawal by Subject	3	5	8
Overall Study Non compliance with protocol	2	0	0
Overall Study Other reasons not stated above	5	2	3
Overall Study Lack of Efficacy	10	5	2

Baseline Characteristics

12 / 48 wk Pivotal PFT vs PBO in COPD II

Baseline characteristics by cohort

Measure	Placebo n=216 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=209 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=217 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Total n=642 Participants Total of all reporting groups
Age, Continuous	63.8 years STANDARD_DEVIATION 8.3 • n=5 Participants	64.7 years STANDARD_DEVIATION 8.1 • n=7 Participants	65.4 years STANDARD_DEVIATION 9.7 • n=5 Participants	64.6 years STANDARD_DEVIATION 8.8 • n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	57 Participants n=7 Participants	65 Participants n=5 Participants	186 Participants n=4 Participants
Sex: Female, Male Male	152 Participants n=5 Participants	152 Participants n=7 Participants	152 Participants n=5 Participants	456 Participants n=4 Participants
Tiotropium (Tio) Use Stratum Non-tiotropium	175 Number of participants n=5 Participants	170 Number of participants n=7 Participants	173 Number of participants n=5 Participants	518 Number of participants n=4 Participants
Tiotropium (Tio) Use Stratum Tiotropium	41 Number of participants n=5 Participants	39 Number of participants n=7 Participants	44 Number of participants n=5 Participants	124 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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)	0.008 Liter Standard Error 0.013	0.159 Liter Standard Error 0.013	0.152 Liter Standard Error 0.013	—	—	—

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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response at Day 85 (12 Weeks)	-0.003 Liter Standard Error 0.014	0.044 Liter Standard Error 0.014	0.045 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=98 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=116 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=107 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)	0.010 Liter Standard Error 0.021	0.120 Liter Standard Error 0.020	0.100 Liter Standard Error 0.020	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.025 Liter Standard Error 0.013	0.189 Liter Standard Error 0.013	0.196 Liter Standard Error 0.013	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.025 Liter Standard Error 0.013	0.188 Liter Standard Error 0.013	0.177 Liter Standard Error 0.013	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.010 Liter Standard Error 0.013	0.180 Liter Standard Error 0.013	0.171 Liter Standard Error 0.013	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	-0.010 Liter Standard Error 0.013	0.155 Liter Standard Error 0.013	0.126 Liter Standard Error 0.013	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	-0.030 Liter Standard Error 0.013	0.132 Liter Standard Error 0.013	0.128 Liter Standard Error 0.013	—	—	—

SECONDARY outcome

Timeframe: 1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 2 Weeks	0.013 Liter Standard Error 0.014	0.066 Liter Standard Error 0.014	0.078 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 6 Weeks	-0.002 Liter Standard Error 0.014	0.071 Liter Standard Error 0.014	0.082 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 18 Weeks	-0.007 Liter Standard Error 0.014	0.062 Liter Standard Error 0.014	0.037 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 24 Weeks	-0.036 Liter Standard Error 0.014	0.033 Liter Standard Error 0.014	0.022 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 32 Weeks	-0.029 Liter Standard Error 0.014	0.029 Liter Standard Error 0.014	-0.002 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 40 Weeks	-0.029 Liter Standard Error 0.014	0.033 Liter Standard Error 0.014	0.043 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FEV1 Response After 48 Weeks	-0.057 Liter Standard Error 0.014	0.011 Liter Standard Error 0.014	0.014 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.099 Liter Standard Error 0.014	0.267 Liter Standard Error 0.014	0.276 Liter Standard Error 0.013	—	—	—

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.104 Liter Standard Error 0.014	0.259 Liter Standard Error 0.014	0.251 Liter Standard Error 0.014	—	—	—

SECONDARY outcome

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

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.080 Liter Standard Error 0.014	0.252 Liter Standard Error 0.014	0.246 Liter Standard Error 0.014	—	—	—

SECONDARY outcome

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

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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.088 Liter Standard Error 0.014	0.232 Liter Standard Error 0.014	0.217 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.062 Liter Standard Error 0.014	0.226 Liter Standard Error 0.014	0.197 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.041 Liter Standard Error 0.014	0.197 Liter Standard Error 0.014	0.198 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.052 Liter Standard Error 0.026	0.383 Liter Standard Error 0.026	0.384 Liter Standard Error 0.026	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.096 Liter Standard Error 0.026	0.338 Liter Standard Error 0.026	0.323 Liter Standard Error 0.026	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.048 Liter Standard Error 0.026	0.312 Liter Standard Error 0.027	0.294 Liter Standard Error 0.026	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.046 Liter Standard Error 0.026	0.284 Liter Standard Error 0.027	0.291 Liter Standard Error 0.026	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.062 Liter Standard Error 0.027	0.303 Liter Standard Error 0.027	0.281 Liter Standard Error 0.026	—	—	—

SECONDARY outcome

Timeframe: 1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.053 Liter Standard Error 0.027	0.271 Liter Standard Error 0.027	0.271 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 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 2 Weeks	0.054 Liter Standard Error 0.028	0.113 Liter Standard Error 0.028	0.141 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 6 Weeks	0.029 Liter Standard Error 0.028	0.122 Liter Standard Error 0.028	0.147 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 12 Weeks	0.043 Liter Standard Error 0.028	0.075 Liter Standard Error 0.028	0.091 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 18 Weeks	0.064 Liter Standard Error 0.028	0.114 Liter Standard Error 0.028	0.098 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 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 24 Weeks	0.021 Liter Standard Error 0.028	0.066 Liter Standard Error 0.028	0.091 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 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 32 Weeks	0.061 Liter Standard Error 0.028	0.099 Liter Standard Error 0.028	0.058 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 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 40 Weeks	0.062 Liter Standard Error 0.028	0.104 Liter Standard Error 0.028	0.131 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=205 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 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
Trough FVC Response After 48 Weeks	-0.008 Liter Standard Error 0.028	0.038 Liter Standard Error 0.028	0.054 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 aftertreatment. 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.202 Liter Standard Error 0.027	0.534 Liter Standard Error 0.028	0.535 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.254 Liter Standard Error 0.027	0.479 Liter Standard Error 0.028	0.464 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.183 Liter Standard Error 0.028	0.451 Liter Standard Error 0.028	0.434 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.213 Liter Standard Error 0.028	0.439 Liter Standard Error 0.028	0.422 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.223 Liter Standard Error 0.028	0.449 Liter Standard Error 0.028	0.429 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 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=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=207 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.208 Liter Standard Error 0.028	0.415 Liter Standard Error 0.028	0.419 Liter Standard Error 0.028	—	—	—

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=98 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=116 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=107 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)	0.057 Liter Standard Error 0.036	0.199 Liter Standard Error 0.035	0.212 Liter Standard Error 0.036	—	—	—

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=211 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=214 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)	182.939 L/min Standard Error 3.800	196.300 L/min Standard Error 3.868	203.873 L/min Standard Error 3.757	—	—	—

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=213 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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)	195.502 L/min Standard Error 3.987	207.958 L/min Standard Error 4.065	216.155 L/min Standard Error 3.948	—	—	—

SECONDARY outcome

Timeframe: 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. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each day during week 48.

Outcome measures

Measure	Placebo n=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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 of Daily Daytime Rescue Use	1.363 Number of puffs Standard Error 0.097	0.947 Number of puffs Standard Error 0.099	0.850 Number of puffs Standard Error 0.097	—	—	—

SECONDARY outcome

Timeframe: 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. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each night during week 48.

Outcome measures

Measure	Placebo n=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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 of Daily Nighttime Rescue Use	2.072 Number of puffs Standard Error 0.121	1.652 Number of puffs Standard Error 0.123	1.312 Number of puffs Standard Error 0.120	—	—	—

SECONDARY outcome

Timeframe: 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. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each 24 hour period during week 48.

Outcome measures

Measure	Placebo n=215 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=205 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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 of Daily (24h) Rescue Use	3.436 Number of puffs Standard Error 0.193	2.599 Number of puffs Standard Error 0.197	2.158 Number of puffs Standard Error 0.192	—	—	—

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=196 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=205 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	3.3 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	2.9 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=196 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=205 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	3.2 Point on scale Standard Error 0.1	2.9 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=196 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=205 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	3.3 Point on scale Standard Error 0.1	3.0 Point on scale Standard Error 0.1	2.9 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=196 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=205 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	3.3 Point on scale Standard Error 0.1	3.1 Point on scale Standard Error 0.1	3.0 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 measured values presented are actually the First Quartile and 95% confidence interval.

Outcome measures

Measure	Placebo n=41 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=175 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=39 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=170 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=44 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=173 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum
Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	306.0 days Interval 98.0 to N/A indicates this statistic was not available due to the low number N/A indicates this statistic was not available due to the low number of events observed	259.0 days Interval 169.0 to N/A indicates this statistic was not available due to the low number of events observed	225.0 days Interval 41.0 to 336.0	315.0 days Interval 196.0 to N/A indicates this statistic was not available due to the low number of events observed	219.0 days Interval 74.0 to 327.0	216.0 days Interval 170.0 to 307.0

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 measured values presented are actually the First Quartile and 95% confidence interval.

Outcome measures

Measure	Placebo n=41 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=175 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=39 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=170 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=44 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=173 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 Interval 305.0 to 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

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. Moderate exacerbations were defined as exacerbations which 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 measured values presented are actually the First Quartile and 95% confidence interval..

Outcome measures

Measure	Placebo n=41 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=175 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=39 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 5 mcg qd (Non-tiotropium) n=170 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olo 10 mcg qd (Tiotropium) n=44 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olo 10 mcg qd(Non-tiotropium) n=173 Participants Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum
Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	NA days Interval 211.0 to N/A indicates this statistic was not available due to the low number of events observed	362.0 days Interval 226.0 to N/A indicates this statistic was not available due to the low number of events observed	NA days Interval 65.0 to N/A indicates this statistic was not available due to the low number of events observed	NA days Interval 235.0 to N/A indicates this statistic was not available due to the low number of events observed	225.0 days Interval 111.0 to N/A indicates this statistic was not available due to the low number of events observed	308.0 days Interval 208.0 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

Mean number of COPD exacerbations per patient years. 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=216 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=209 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=217 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	0.4590 COPD exacerbations Standard Error 0.0687	0.5453 COPD exacerbations Standard Error 0.0765	0.5885 COPD exacerbations Standard Error 0.0799	—	—	—

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

Mean number of COPD exacerbations requiring hospitalization per patient years. 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=216 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=209 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=217 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	0.0786 COPD exacerbations Standard Error 0.0273	0.0811 COPD exacerbations Standard Error 0.0268	0.0886 COPD exacerbations Standard Error 0.0287	—	—	—

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

Mean number of moderate COPD exacerbations per patient years. 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. Moderate exacerbations were defined as exacerbations which did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.

Outcome measures

Measure	Placebo n=216 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=209 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=215 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	0.3375 COPD exacerbations Standard Error 0.0587	0.4335 COPD exacerbations Standard Error 0.0699	0.4513 COPD exacerbations Standard Error 0.0701	—	—	—

SECONDARY outcome

Timeframe: 48 weeks

Population: Treated set.

Occurence 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=216 Participants Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg qd n=209 Participants Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg qd n=217 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	13.9 percentage of participants	3.3 percentage of participants	5.5 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Blood glucose increased	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	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Ventricular tachycardia	0.0 percentage of participants	1.9 percentage of participants	0.5 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Ventricular extrasystoles	0.0 percentage of participants	1.0 percentage of participants	1.8 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Supraventricular extrasystoles	0.0 percentage of participants	1.0 percentage of participants	1.4 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Atrial fibrillation	0.5 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Atrioventricular block	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Atrioventricular block first degree	0.0 percentage of participants	0.5 percentage of participants	0.5 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Atrioventricular block second degree	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Bundle branch block left	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Palpitations	0.0 percentage of participants	0.0 percentage of participants	0.5 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Sinus bradycardia	0.0 percentage of participants	0.5 percentage of participants	0.0 percentage of participants	—	—	—
Changes in Safety Parameters Related to Treatment Sinus tachycardia	0.0 percentage of participants	0.5 percentage of participants	0.0 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=207 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=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
Change From Baseline in Potassium	-0.0 mmol/L Standard Deviation 0.4	-0.0 mmol/L Standard Deviation 0.4	0.0 mmol/L Standard Deviation 0.3	—	—	—

Adverse Events

Placebo

Serious events: 32 serious events

Other events: 75 other events

Deaths: 0 deaths

Olo 5 mcg

Serious events: 32 serious events

Other events: 71 other events

Deaths: 0 deaths

Olo 10 mcg

Serious events: 37 serious events

Other events: 81 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=216 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg n=209 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=217 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Cardiac disorders Acute myocardial infarction	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Cardiac disorders Atrial fibrillation	0.46% 1/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Atrial flutter	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Bradycardia	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Cardiac failure congestive	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Coronary artery disease	0.46% 1/216 • 48 weeks	0.96% 2/209 • 48 weeks	0.46% 1/217 • 48 weeks
Cardiac disorders Coronary artery occlusion	0.46% 1/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Coronary artery stenosis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Cardiac disorders Left ventricular dysfunction	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Myocardial infarction	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Cardiac disorders Ventricular tachycardia	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Eye disorders Lens dislocation	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Eye disorders Retinal detachment	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Abdominal pain	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Gastrointestinal disorders Colitis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Diarrhoea	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Gastrointestinal disorders Gastric polyps	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Hiatus hernia	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Inguinal hernia	0.46% 1/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Gastrointestinal disorders Intestinal perforation	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Gastrointestinal disorders Oesophageal rupture	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
General disorders Chest discomfort	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
General disorders Chest pain	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
General disorders Pyrexia	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
General disorders Sudden cardiac death	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Hepatobiliary disorders Cholecystitis	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Hepatobiliary disorders Cholecystitis acute	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Immune system disorders Contrast media allergy	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Infections and infestations Helicobacter gastritis	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Infections and infestations Infective exacerbation of chronic obstructive airways disease	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Infections and infestations Lung infection	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.92% 2/217 • 48 weeks
Infections and infestations Oesophageal candidiasis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Infections and infestations Pneumonia	1.9% 4/216 • 48 weeks	1.4% 3/209 • 48 weeks	2.3% 5/217 • 48 weeks
Infections and infestations Pneumonia legionella	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Infections and infestations Pneumonia staphylococcal	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Infections and infestations Staphylococcal sepsis	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Injury, poisoning and procedural complications Fall	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Injury, poisoning and procedural complications Hip fracture	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Injury	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Injury, poisoning and procedural complications Overdose	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Rib fracture	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Road traffic accident	0.46% 1/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.46% 1/217 • 48 weeks
Injury, poisoning and procedural complications Spinal compression fracture	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Injury, poisoning and procedural complications Subdural haemorrhage	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Metabolism and nutrition disorders Dehydration	0.00% 0/216 • 48 weeks	0.96% 2/209 • 48 weeks	0.00% 0/217 • 48 weeks
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.92% 2/217 • 48 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc degeneration	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.46% 1/217 • 48 weeks
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Musculoskeletal and connective tissue disorders Spinal column stenosis	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Musculoskeletal and connective tissue disorders Spinal osteoarthritis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal cell carcinoma	0.46% 1/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hypopharyngeal cancer	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Keratoacanthoma	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer stage unspecified	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Nervous system disorders Carotid artery disease	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Nervous system disorders Cerebrovascular accident	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Nervous system disorders Subarachnoid haemorrhage	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Nervous system disorders Transient ischaemic attack	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Nervous system disorders VIth nerve paralysis	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Reproductive system and breast disorders Benign prostatic hyperplasia	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Reproductive system and breast disorders Prostatomegaly	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.46% 1/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.6% 12/216 • 48 weeks	3.3% 7/209 • 48 weeks	5.5% 12/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.00% 0/216 • 48 weeks	0.48% 1/209 • 48 weeks	0.00% 0/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Hypercapnia	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Nasal septum deviation	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.93% 2/216 • 48 weeks	0.96% 2/209 • 48 weeks	0.46% 1/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Respiratory acidosis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	1.4% 3/217 • 48 weeks
Vascular disorders Aortic aneurysm	0.00% 0/216 • 48 weeks	1.4% 3/209 • 48 weeks	0.00% 0/217 • 48 weeks
Vascular disorders Deep vein thrombosis	0.00% 0/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.46% 1/217 • 48 weeks
Vascular disorders Hypotension	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks
Vascular disorders Peripheral vascular disorder	0.46% 1/216 • 48 weeks	0.00% 0/209 • 48 weeks	0.00% 0/217 • 48 weeks

Other adverse events

Measure	Placebo n=216 participants at risk Matching Placebo delivered by the Respimat Inhaler.	Olo 5 mcg n=209 participants at risk Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olo 10 mcg n=217 participants at risk Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.
Infections and infestations Nasopharyngitis	8.3% 18/216 • 48 weeks	9.1% 19/209 • 48 weeks	11.5% 25/217 • 48 weeks
Infections and infestations Upper respiratory tract infection	7.9% 17/216 • 48 weeks	9.6% 20/209 • 48 weeks	10.1% 22/217 • 48 weeks
Nervous system disorders Headache	5.1% 11/216 • 48 weeks	3.3% 7/209 • 48 weeks	1.8% 4/217 • 48 weeks
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	19.9% 43/216 • 48 weeks	18.7% 39/209 • 48 weeks	21.7% 47/217 • 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