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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00793624
• Collaborator: (none)
• Enrollment: 906
• Locations: 93
• Arms: 4
• Patients Per Site: 9.7

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the long-term efficacy and safety of once daily treatment of BI 1744 CL inhalation solution (5 and 10 mcg) delivered via the Respimat® inhaler, in patients with COPD.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: Olodaterol (BI 1744); Drug: Olodaterol (BI 1744); Drug: Formoterol; Drug: Placebo; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 906 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel Group Study to Assess the Efficacy and Safety of 48 Weeks of Once Daily Treatment of Orally Inhaled BI 1744 CL (5 µg [2 Actuations of 2.5 ug] and 10 ug [2 Actuations of 5 ug]) Delivered by the Respimat® Inhaler, and 48 Weeks of Twice Daily Foradil® (12 µg) Delivered by the Aerolizer® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Feb 1, 2009
• Actual Primary Completion Date: Dec 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Olodaterol (BI 1744) Low Low dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI 1744); Comparison of low and high doses on efficacy and safety in COPD patients
Experimental: Olodaterol (BI 1744) High High dose inhaled orally once daily from the Respimat inhaler	Drug: Olodaterol (BI 1744); Comparison of low and high doses on efficacy and safety in COPD patients
Active Comparator: Formoterol 12mcg 12mcg inhaled twice daily from the Aerolizer inhaler	Drug: Formoterol; Active comparator with Olodaterol (BI 1744) on safety and efficacy in COPD patients
Placebo Comparator: Placebo Olodaterol (BI 1744) placebo inhaled once daily from the Respimat inhaler and/or Formoterol placebo inhaled twice daily from the Aerolizer inhaler	Drug: Placebo; Placebo for comparison with Olodaterol (BI 1744) on safety and efficacy in COPD patients; Drug: Placebo; Placebo for comparison Formoterolon safety and efficacy in COPD patients

Outcome Measures

Primary Outcome Measures

1. Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24]

   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.

2. Trough FEV1 Response at Week 24 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.]

   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.

3. Mahler Transitional Dyspnea Index Focal Score at 24 Weeks [Baseline, Week 24]

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

4. Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis [Baseline, Week 24]

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

Secondary Outcome Measures

1. Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks [Baseline, Week 24]

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

2. Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks [Baseline, Week 12]

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

3. Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks [Baseline, Week 48]

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

4. Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis [Baseline, Week 24]

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

5. Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2]

   Response was defined as change from baseline. Baseline 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.

6. Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6]

   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.

7. Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12]

   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.

8. Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48]

   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.

9. Trough FEV1 Response at Week 2 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.]

   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.

10. Trough FEV1 Response at Week 6 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.]

    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.

11. Trough FEV1 Response at Week 12 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.]

    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.

12. Trough FEV1 Response at Week 18 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.]

    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.

13. Trough FEV1 Response at Week 32 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.]

    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.

14. Trough FEV1 Response at Week 40 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.]

    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.

15. Trough FEV1 Response at Week 48 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.]

    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.

16. Peak FEV1 (0-3h) Response After 2 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks]

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

17. Peak FEV1 (0-3h) Response After 6 Weeks [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]

    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.

18. Peak FEV1 (0-3h) Response After 12 Weeks [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]

    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.

19. Peak FEV1 (0-3h) Response After 24 Weeks [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]

    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.

20. Peak FEV1 (0-3h) Response After 48 Weeks [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]

    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.

21. Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2]

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

22. Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6]

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

23. Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12]

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

24. Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24]

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

25. Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48]

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

26. Trough FVC Response at Week 2 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.]

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

27. Trough FVC Response at Week 6 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.]

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

28. Trough FVC Response at Week 12 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.]

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

29. Trough FVC Response at Week 18 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.]

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

30. Trough FVC Response at Week 24 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.]

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

31. Trough FVC Response at Week 32 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.]

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

32. Trough FVC Response at Week 48 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.]

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

33. Trough FVC Response at Week 40 [1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.]

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

34. Peak FVC (0-3h) Response After 2 Weeks [1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 2 weeks]

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

35. Peak FVC (0-3h) Response After 6 Weeks [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]

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

36. Peak FVC (0-3h) Response After 12 Weeks [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]

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

37. Peak FVC (0-3h) Response After 24 Weeks [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]

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

38. Peak FVC (0-3h) Response After 48 Weeks [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]

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

39. Peak Expiratory Flow Rate (PEFR) at Week 24 [Week 24]

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

40. Use of Rescue Medication at Week 24 [Week 24]

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

41. Patient's Global Rating (PGR) at 6 Weeks [Week 6]

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

42. Patient's Global Rating (PGR) at 12 Weeks [Week 12]

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

43. Patient's Global Rating (PGR) at 24 Weeks [Week 24]

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

44. Patient's Global Rating (PGR) at 48 Weeks [Week 48]

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

45. Mahler Transitional Dyspnea Index Focal Score at 6 Weeks [Baseline, Week 6]

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

46. Mahler Transitional Dyspnea Index Focal Score at 12 Weeks [Baseline, Week 12]

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

47. Mahler Transitional Dyspnea Index Focal Score at 18 Weeks [Baseline, Week 18]

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

48. Mahler Transitional Dyspnea Index Focal Score at 32 Weeks [Baseline, Week 32]

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

49. Mahler Transitional Dyspnea Index Focal Score at 40 Weeks [Baseline, Week 40]

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

50. Mahler Transitional Dyspnea Index Focal Score at 48 Weeks [Baseline, Week 48]

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

51. Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation [Baseline to end of study at 48 weeks.]

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

52. Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization [Baseline to end of study at 48 weeks.]

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

53. Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation [Baseline to end of study at 48 weeks.]

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

54. Number of COPD Exacerbations [Baseline to end of study at week 48 visit]

    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.

55. Number of COPD Exacerbations Requiring Hospitalization [Baseline to end of study at week 48 visit]

    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.

56. Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations [Baseline to end of study at 48 weeks.]

    Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.

57. Absolute Plasma Concentrations [within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18]

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

58. Changes in Safety Parameters Related to Treatment [48 weeks]

    Occurence of cardiac disorders and investigations related to treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. All patients must have a diagnosis of chronic obstructive pulmonary disease and must meet the following spirometric criteria:post-bronchodilator FEV1<80% of predicted normal (ECSC) and a post-bronchodilator FEV1/FVC <70% at Visit 1

2. Male or female patients, 40 years of age or older

3. Patients must be current or ex-smokers with a smoking history of more than 10 pack years:

Exclusion criteria:

1. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or urinalysis; all patients with an SGOT >x2 ULN, SGPT >x2 ULN, bilirubin >x2 ULN or creatinine >x2 ULN

2. Patients with a history of asthma and/or total blood eosinophil count greater than 600/mm3

3. Patients with thyrotoxicosis, paroxysmal tachycardia (>100 beats per minute)

4. Patients with a history of myocardial infarction within 1 year of screening visit, unstable or life-threatening cardiac arrhythmia, hospitalization for heart failure within the past year, known active tuberculosis, a malignancy for which patient has undergone resection, radiation therapy or chemotherapy within last five years, life-threatening pulmonary obstruction, cystic fibrosis, clinically evident bronchiectasis, significant alcohol or drug abuse

5. Patients who have undergone thoracotomy with pulmonary resection

6. Patients being treated with oral beta-adrenergics or oral corticosteroid medication at unstable doses (i.e., less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per day or 20 mg every other day.

7. Patients who regularly use daytime oxygen therapy for more than one hour per day.

8. Patients who have completed a pulmonary rehabilitation program in the six weeks prior to the screening visit (Visit 1) or patients who are currently in a pulmonary rehabilitation program

9. Pregnant or nursing women

10. Women of childbearing potential not using two effective methods of birth control (one barrier and one non-barrier).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1222.13.2401 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
2	1222.13.2403 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
3	1222.13.2402 Boehringer Ingelheim Investigational Site	Mar del Plata		Argentina
4	1222.13.2404 Boehringer Ingelheim Investigational Site	Monte Grande		Argentina
5	1222.13.2502 Boehringer Ingelheim Investigational Site	Juiz de Fora		Brazil
6	1222.13.2503 Boehringer Ingelheim Investigational Site	Rio de Janeiro		Brazil
7	1222.13.2505 Boehringer Ingelheim Investigational Site	Rio de Janeiro		Brazil
8	1222.13.2501 Boehringer Ingelheim Investigational Site	Sao Paulo		Brazil
9	1222.13.2504 Boehringer Ingelheim Investigational Site	Sao Paulo		Brazil
10	1222.13.1408 Boehringer Ingelheim Investigational Site	Calgary	Alberta	Canada
11	1222.13.1407 Boehringer Ingelheim Investigational Site	Chilliwack	British Columbia	Canada
12	1222.13.1403 Boehringer Ingelheim Investigational Site	Downsview	Ontario	Canada
13	1222.13.1412 Boehringer Ingelheim Investigational Site	Hamilton	Ontario	Canada
14	1222.13.1401 Boehringer Ingelheim Investigational Site	Niagara Falls	Ontario	Canada
15	1222.13.1410 Boehringer Ingelheim Investigational Site	Sarnia	Ontario	Canada
16	1222.13.1413 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
17	1222.13.1404 Boehringer Ingelheim Investigational Site	La Malbaie	Quebec	Canada
18	1222.13.1411 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
19	1222.13.1406 Boehringer Ingelheim Investigational Site	Point Claire	Quebec	Canada
20	1222.13.1402 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan	Canada
21	1222.13.3502 Boehringer Ingelheim Investigational Site	Dubrovnik		Croatia
22	1222.13.3503 Boehringer Ingelheim Investigational Site	Rijeka		Croatia
23	1222.13.3504 Boehringer Ingelheim Investigational Site	Split		Croatia
24	1222.13.3501 Boehringer Ingelheim Investigational Site	Zagreb		Croatia
25	1222.13.3401 Boehringer Ingelheim Investigational Site	Beroun		Czech Republic
26	1222.13.3403 Boehringer Ingelheim Investigational Site	Cesky Tesin		Czech Republic
27	1222.13.3402 Boehringer Ingelheim Investigational Site	Tabor		Czech Republic
28	1222.13.2003 Boehringer Ingelheim Investigational Site	Aalborg		Denmark
29	1222.13.2002 Boehringer Ingelheim Investigational Site	Hvidovre		Denmark
30	1222.13.2001 Boehringer Ingelheim Investigational Site	Silkeborg		Denmark
31	1222.13.2103 Boehringer Ingelheim Investigational Site	Lahti		Finland
32	1222.13.2101 Boehringer Ingelheim Investigational Site	Tampere		Finland
33	1222.13.2102 Boehringer Ingelheim Investigational Site	Turku		Finland
34	1222.13.1502 Boehringer Ingelheim Investigational Site	Berlin		Germany
35	1222.13.1503 Boehringer Ingelheim Investigational Site	Berlin		Germany
36	1222.13.1506 Boehringer Ingelheim Investigational Site	Berlin		Germany
37	1222.13.1511 Boehringer Ingelheim Investigational Site	Dortmund		Germany
38	1222.13.1514 Boehringer Ingelheim Investigational Site	Essen		Germany
39	1222.13.1509 Boehringer Ingelheim Investigational Site	Großhansdorf		Germany
40	1222.13.1508 Boehringer Ingelheim Investigational Site	Hannover		Germany
41	1222.13.1510 Boehringer Ingelheim Investigational Site	Hannover		Germany
42	1222.13.1512 Boehringer Ingelheim Investigational Site	Kiel		Germany
43	1222.13.1501 Boehringer Ingelheim Investigational Site	Köln		Germany
44	1222.13.1505 Boehringer Ingelheim Investigational Site	Reinfeld		Germany
45	1222.13.1507 Boehringer Ingelheim Investigational Site	Schwerin		Germany
46	1222.13.2901 Boehringer Ingelheim Investigational Site	Kowloon		Hong Kong
47	1222.13.2804 Boehringer Ingelheim Investigational Site	Bangalore		India
48	1222.13.2803 Boehringer Ingelheim Investigational Site	Chennai		India
49	1222.13.2806 Boehringer Ingelheim Investigational Site	Coimbatore-		India
50	1222.13.2810 Boehringer Ingelheim Investigational Site	Hyderabad		India
51	1222.13.2801 Boehringer Ingelheim Investigational Site	Indore		India
52	1222.13.2807 Boehringer Ingelheim Investigational Site	Indore		India
53	1222.13.2805 Boehringer Ingelheim Investigational Site	Jaipur		India
54	1222.13.2802 Boehringer Ingelheim Investigational Site	Ludhiana, Punjab		India
55	1222.13.2809 Boehringer Ingelheim Investigational Site	Mumbai		India
56	1222.13.2812 Boehringer Ingelheim Investigational Site	Mumbai		India
57	1222.13.2811 Boehringer Ingelheim Investigational Site	Pune		India
58	1222.13.1704 Boehringer Ingelheim Investigational Site	Catania		Italy
59	1222.13.1702 Boehringer Ingelheim Investigational Site	Genova		Italy
60	1222.13.1701 Boehringer Ingelheim Investigational Site	Pisa		Italy
61	1222.13.1705 Boehringer Ingelheim Investigational Site	Siena		Italy
62	1222.13.1703 Boehringer Ingelheim Investigational Site	Trieste		Italy
63	1222.13.2701 Boehringer Ingelheim Investigational Site	Gwangju		Korea, Republic of
64	1222.13.2702 Boehringer Ingelheim Investigational Site	Incheon		Korea, Republic of
65	1222.13.2703 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
66	1222.13.2705 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
67	1222.13.2706 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
68	1222.13.2704 Boehringer Ingelheim Investigational Site	Suwon		Korea, Republic of
69	1222.13.3103 Boehringer Ingelheim Investigational Site	Batu Caves		Malaysia
70	1222.13.3101 Boehringer Ingelheim Investigational Site	Kota Kinabalu		Malaysia
71	1222.13.3102 Boehringer Ingelheim Investigational Site	Kuala Lumpur		Malaysia
72	1222.13.3104 Boehringer Ingelheim Investigational Site	Kuantan		Malaysia
73	1222.13.2201 Boehringer Ingelheim Investigational Site	Bergen		Norway
74	1222.13.2202 Boehringer Ingelheim Investigational Site	Oslo		Norway
75	1222.13.3203 Boehringer Ingelheim Investigational Site	Cebu		Philippines
76	1222.13.3201 Boehringer Ingelheim Investigational Site	Quezon City		Philippines
77	1222.13.3202 Boehringer Ingelheim Investigational Site	Quezon City		Philippines
78	1222.13.2302 Boehringer Ingelheim Investigational Site	Durban		South Africa
79	1222.13.2301 Boehringer Ingelheim Investigational Site	Pretoria		South Africa
80	1222.13.1803 Boehringer Ingelheim Investigational Site	Aranjuez		Spain
81	1222.13.1806 Boehringer Ingelheim Investigational Site	Elda		Spain
82	1222.13.1802 Boehringer Ingelheim Investigational Site	Els Hostalets de Balenyà		Spain
83	1222.13.1804 Boehringer Ingelheim Investigational Site	Pozuelo de Alarcón		Spain
84	1222.13.1805 Boehringer Ingelheim Investigational Site	Valladolid		Spain
85	1222.13.1801 Boehringer Ingelheim Investigational Site	Vic (Barcelona)		Spain
86	1222.13.1901 Boehringer Ingelheim Investigational Site	Boden		Sweden
87	1222.13.1902 Boehringer Ingelheim Investigational Site	Sundsvall		Sweden
88	1222.13.3302 Boehringer Ingelheim Investigational Site	Bangkok		Thailand
89	1222.13.3303 Boehringer Ingelheim Investigational Site	Bangkok		Thailand
90	1222.13.3301 Boehringer Ingelheim Investigational Site	Chiang Mai		Thailand
91	1222.13.3602 Boehringer Ingelheim Investigational Site	Ivano-Frankivsk		Ukraine
92	1222.13.3601 Boehringer Ingelheim Investigational Site	Kharkiv		Ukraine
93	1222.13.3603 Boehringer Ingelheim Investigational Site	Kiev		Ukraine

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00793624
• Other Study ID Numbers: 1222.13; 2008-001933-84
• First Posted: Nov 19, 2008
• Last Update Posted: Jun 27, 2014
• Last Verified: Jun 1, 2014

• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Formoterol Fumarate; Olodaterol

Study Results

Participant Flow

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

Arm/Group Title	Placebo	Olodaterol (Olo) 5 mcg qd	Olodaterol (Olo) 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Period Title: Overall Study
STARTED	225	227	225	227
COMPLETED	168	191	186	184
NOT COMPLETED	57	36	39	43

Baseline Characteristics

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg	Total
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.	Total of all reporting groups
Overall Participants	225	227	225	227	904
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.0 (8.4)	63.7 (9.1)	62.6 (8.8)	64.8 (8.6)	63.8 (8.7)
Sex: Female, Male (Count of Participants)
Female	45 20%	50 22%	55 24.4%	48 21.1%	198 21.9%
Male	180 80%	177 78%	170 75.6%	179 78.9%	706 78.1%
Tiotropium (Tio) Use Stratum (Number of participants) [Number]
Non-tiotropium	169 75.1%	168 74%	167 74.2%	169 74.4%	673 74.4%
Tiotropium	56 24.9%	59 26%	58 25.8%	58 25.6%	231 25.6%

Outcome Measures

1. Primary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	-0.009 (0.016)	0.142 (0.015)	0.156 (0.015)	0.168 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.151
	Confidence Interval	() 95%; 0.110 to 0.193
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.165
	Confidence Interval	() 95%; 0.124 to 0.206
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.177
	Confidence Interval	() 95%; 0.136 to 0.218
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

2. Primary Outcome

Title	Trough FEV1 Response at Week 24
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.056 (0.015)	0.021 (0.015)	0.028 (0.015)	-0.002 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.078
	Confidence Interval	() 95%; 0.037 to 0.118
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.085
	Confidence Interval	() 95%; 0.044 to 0.125
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0088
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.054
	Confidence Interval	() 95%; 0.014 to 0.095
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

3. Primary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 24 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	2.046 (0.255)	2.234 (0.240)	2.068 (0.245)	1.818 (0.247)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5843
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.188
	Confidence Interval	() 95%; -0.485 to 0.860
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.343
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9494
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.022
	Confidence Interval	() 95%; -0.656 to 0.699
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.345
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5099
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.288
	Confidence Interval	() 95%; -0.908 to 0.451
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.346
	Estimation Comments	Form 12 mcg minus Placebo

4. Secondary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks
Description	Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	185	200	202	202
Least Squares Mean (Standard Error) [score on a scale]	41.068 (1.038)	38.627 (0.995)	37.674 (0.998)	40.116 (0.994)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0816
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.442
	Confidence Interval	() 95%; -5.190 to 0.307
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.401
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0155
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.394
	Confidence Interval	() 95%; -6.141 to -0.648
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.400
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4954
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.952
	Confidence Interval	() 95%; -3.691 to 1.787
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.396
	Estimation Comments	Form 12 mcg minus Placebo

5. Secondary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Total Score at 12 Weeks
Description	Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	185	200	202	202
Least Squares Mean (Standard Error) [score on a scale]	42.105 (1.027)	39.320 (0.986)	36.961 (0.989)	40.351 (0.992)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0450
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.785
	Confidence Interval	() 95%; -5.507 to -0.063
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.387
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.144
	Confidence Interval	() 95%; -7.864 to -2.425
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.386
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2061
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.754
	Confidence Interval	() 95%; -4.474 to 0.966
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.386
	Estimation Comments	Form 12 mcg minus Placebo

6. Secondary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Total Score at 48 Weeks
Description	Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	185	200	202	202
Least Squares Mean (Standard Error) [score on a scale]	40.415 (1.057)	38.545 (1.000)	36.850 (1.015)	40.431 (1.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1878
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.871
	Confidence Interval	() 95%; -4.655 to 0.914
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.419
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0126
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.565
	Confidence Interval	() 95%; -6.364 to -0.767
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.427
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9913
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.016
	Confidence Interval	() 95%; -2.782 to 2.814
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.426
	Estimation Comments	Form 12 mcg minus Placebo

7. Secondary Outcome

Title	Saint George's Respiratory Questionnaire (SGRQ) Total Score at 24 Weeks for Combined Analysis
Description	Saint George's Respiratory Questionnaire (SGRQ) measures the impact of COPD on overall health, daily life, and perceived well-being ranging from 0 (no limitations) to 100 (most limitations). This is a combined analysis of the data from NCT00793624 and NCT00796653 showing adjusted values using a MMRM model.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	387	416	414	408
Mean (Standard Error) [score on a scale]	41.639 (0.718)	38.794 (0.693)	38.205 (0.695)	40.391 (0.699)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Olo 5 mcg qd minus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.846
	Confidence Interval	() 95%; -4.751 to -0.940
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.972
	Estimation Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Olo 10 mcg qd minus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0004
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.434
	Confidence Interval	() 95%; -5.343 to -1.525
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.973
	Estimation Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Form 10 mcg qd minus Placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2009
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.248
	Confidence Interval	() 95%; -3.161 to 0.665
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.976
	Estimation Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect

8. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.015 (0.015)	0.201 (0.015)	0.181 (0.015)	0.221 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.186
	Confidence Interval	() 95%; 0.146 to 0.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.166
	Confidence Interval	() 95%; 0.126 to 0.206
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.206
	Confidence Interval	() 95%; 0.166 to 0.246
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Form 12 mcg minus Placebo

9. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.001 (0.015)	0.178 (0.015)	0.161 (0.015)	0.194 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.176
	Confidence Interval	() 95%; 0.136 to 0.217
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.160
	Confidence Interval	() 95%; 0.119 to 0.200
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.192
	Confidence Interval	() 95%; 0.152 to 0.233
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

10. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	-0.003 (0.015)	0.176 (0.015)	0.167 (0.015)	0.182 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.178
	Confidence Interval	() 95%; 0.137 to 0.219
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.170
	Confidence Interval	() 95%; 0.129 to 0.211
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.185
	Confidence Interval	() 95%; 0.144 to 0.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

11. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	-0.023 (0.016)	0.122 (0.015)	0.123 (0.015)	0.149 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.145
	Confidence Interval	() 95%; 0.103 to 0.186
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.146
	Confidence Interval	() 95%; 0.105 to 0.188
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.172
	Confidence Interval	() 95%; 0.130 to 0.214
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

12. Secondary Outcome

Title	Trough FEV1 Response at Week 2
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.019 (0.015)	0.068 (0.014)	0.060 (0.014)	0.061 (0.014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.087
	Confidence Interval	() 95%; 0.048 to 0.126
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.079
	Confidence Interval	() 95%; 0.040 to 0.118
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.080
	Confidence Interval	() 95%; 0.040 to 0.119
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Form 12 mcg minus Placebo

13. Secondary Outcome

Title	Trough FEV1 Response at Week 6
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.037 (0.015)	0.049 (0.014)	0.041 (0.014)	0.042 (0.014)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.086
	Confidence Interval	() 95%; 0.047 to 0.125
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.078
	Confidence Interval	() 95%; 0.038 to 0.117
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.079
	Confidence Interval	() 95%; 0.039 to 0.119
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Form 12 mcg minus Placebo

14. Secondary Outcome

Title	Trough FEV1 Response at Week 12
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.027 (0.015)	0.056 (0.014)	0.048 (0.014)	0.033 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.083
	Confidence Interval	() 95%; 0.043 to 0.123
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.075
	Confidence Interval	() 95%; 0.035 to 0.114
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0037
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.059
	Confidence Interval	() 95%; 0.019 to 0.100
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Form 12 mcg minus Placebo

15. Secondary Outcome

Title	Trough FEV1 Response at Week 18
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.019 (0.015)	0.046 (0.014)	0.026 (0.015)	0.023 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0016
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.065
	Confidence Interval	() 95%; 0.025 to 0.105
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0276
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.045
	Confidence Interval	() 95%; 0.005 to 0.085
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0426
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.042
	Confidence Interval	() 95%; 0.001 to 0.082
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

16. Secondary Outcome

Title	Trough FEV1 Response at Week 32
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.023 (0.015)	0.023 (0.015)	0.026 (0.015)	0.021 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0237
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.047
	Confidence Interval	() 95%; 0.006 to 0.087
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0175
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.049
	Confidence Interval	() 95%; 0.009 to 0.090
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0339
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.044
	Confidence Interval	() 95%; 0.003 to 0.085
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

17. Secondary Outcome

Title	Trough FEV1 Response at Week 40
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.020 (0.016)	0.020 (0.015)	0.017 (0.015)	0.004 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0537
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.040
	Confidence Interval	() 95%; -0.001 to 0.081
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0808
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.037
	Confidence Interval	() 95%; -0.004 to 0.078
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2579
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.024
	Confidence Interval	() 95%; -0.017 to 0.065
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Form 12 mcg minus Placebo

18. Secondary Outcome

Title	Trough FEV1 Response at Week 48
Description	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.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.065 (0.015)	0.003 (0.015)	-0.009 (0.015)	-0.006 (0.015)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0011
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.068
	Confidence Interval	() 95%; 0.027 to 0.109
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0069
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.059
	Confidence Interval	() 95%; 0.018 to 0.101
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.021
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.080
	Confidence Interval	() 95%; 0.040 to 0.119
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	Estimation Comments	Form 12 mcg minus Placebo

19. Secondary Outcome

Title	Peak FEV1 (0-3h) Response After 2 Weeks
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.100 (0.016)	0.277 (0.016)	0.250 (0.016)	0.290 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.177
	Confidence Interval	() 95%; 0.135 to 0.220
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.150
	Confidence Interval	() 95%; 0.108 to 0.193
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.190
	Confidence Interval	() 95%; 0.148 to 0.233
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Form 12 mcg minus Placebo

20. Secondary Outcome

Title	Peak FEV1 (0-3h) Response After 6 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.081 (0.016)	0.248 (0.016)	0.234 (0.016)	0.264 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.166
	Confidence Interval	() 95%; 0.124 to 0.209
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.152
	Confidence Interval	() 95%; 0.109 to 0.195
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.182
	Confidence Interval	() 95%; 0.139 to 0.226
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Form 12 mcg minus Placebo

21. Secondary Outcome

Title	Peak FEV1 (0-3h) Response After 12 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.082 (0.016)	0.247 (0.016)	0.241 (0.016)	0.256 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.165
	Confidence Interval	() 95%; 0.122 to 0.208
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.159
	Confidence Interval	() 95%; 0.116 to 0.203
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.174
	Confidence Interval	() 95%; 0.130 to 0.218
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Form 12 mcg minus Placebo

22. Secondary Outcome

Title	Peak FEV1 (0-3h) Response After 24 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.068 (0.017)	0.216 (0.016)	0.225 (0.016)	0.236 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.148
	Confidence Interval	() 95%; 0.104 to 0.191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.167
	Confidence Interval	() 95%; 0.112 to 0.200
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.167
	Confidence Interval	() 95%; 0.123 to 0.211
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.022
	Estimation Comments	Form 12 mcg minus Placebo

23. Secondary Outcome

Title	Peak FEV1 (0-3h) Response After 48 Weeks
Description	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.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.053 (0.017)	0.192 (0.016)	0.193 (0.016)	0.215 (0.016)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.139
	Confidence Interval	() 95%; 0.095 to 0.183
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.023
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.140
	Confidence Interval	() 95%; 0.095 to 0.184
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.023
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.162
	Confidence Interval	() 95%; 0.117 to 0.206
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.023
	Estimation Comments	Form 12 mcg minus Placebo

24. Secondary Outcome

Title	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 2 Weeks
Description	Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.076 (0.028)	0.299 (0.027)	0.311 (0.027)	0.383 (0.027)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.223
	Confidence Interval	() 95%; 0.149 to 0.297
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.235
	Confidence Interval	() 95%; 0.161 to 0.309
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.307
	Confidence Interval	() 95%; 0.233 to 0.381
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Form 12 mcg minus Placebo

25. Secondary Outcome

Title	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 6 Weeks
Description	Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.016 (0.028)	0.252 (0.027)	0.265 (0.027)	0.326 (0.027)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.236
	Confidence Interval	() 95%; 0.161 to 0.310
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.249
	Confidence Interval	() 95%; 0.175 to 0.324
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.310
	Confidence Interval	() 95%; 0.235 to 0.384
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Form 12 mcg minus Placebo

26. Secondary Outcome

Title	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 12 Weeks
Description	Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.023 (0.028)	0.233 (0.027)	0.278 (0.027)	0.300 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.210
	Confidence Interval	() 95%; 0.135 to 0.285
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.254
	Confidence Interval	() 95%; 0.179 to 0.329
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.276
	Confidence Interval	() 95%; 0.201 to 0.352
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

27. Secondary Outcome

Title	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 24 Weeks
Description	Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.037 (0.029)	0.220 (0.027)	0.252 (0.028)	0.279 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.182
	Confidence Interval	() 95%; 0.107 to 0.258
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.215
	Confidence Interval	() 95%; 0.139 to 0.291
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.242
	Confidence Interval	() 95%; 0.166 to 0.318
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

28. Secondary Outcome

Title	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at 48 Weeks
Description	Response was defined as change from baseline. Baseline FVC was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first am dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose on Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.016 (0.029)	0.196 (0.028)	0.219 (0.028)	0.260 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.179
	Confidence Interval	() 95%; 0.103 to 0.256
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.203
	Confidence Interval	() 95%; 0.126 to 0.280
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.243
	Confidence Interval	() 95%; 0.166 to 0.320
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

29. Secondary Outcome

Title	Trough FVC Response at Week 2
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 2.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	0.042 (0.028)	0.110 (0.027)	0.119 (0.028)	0.126 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0781
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.068
	Confidence Interval	() 95%; -0.008 to 0.143
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0455
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.077
	Confidence Interval	() 95%; 0.002 to 0.153
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0290
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.085
	Confidence Interval	() 95%; 0.009 to 0.160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

30. Secondary Outcome

Title	Trough FVC Response at Week 6
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 6.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.046 (0.029)	0.065 (0.027)	0.085 (0.028)	0.090 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0043
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.110
	Confidence Interval	() 95%; 0.035 to 0.186
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.131
	Confidence Interval	() 95%; 0.055 to 0.207
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.136
	Confidence Interval	() 95%; 0.060 to 0.212
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

31. Secondary Outcome

Title	Trough FVC Response at Week 12
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 12.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.018 (0.029)	0.079 (0.028)	0.087 (0.028)	0.068 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0136
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.097
	Confidence Interval	() 95%; 0.020 to 0.173
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.105
	Confidence Interval	() 95%; 0.028 to 0.182
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0294
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.086
	Confidence Interval	() 95%; 0.009 to 0.163
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Form 12 mcg minus Placebo

32. Secondary Outcome

Title	Trough FVC Response at Week 18
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 18.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	0.060 (0.029)	0.066 (0.028)	0.078 (0.028)	0.063 (0.028)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8674
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.007
	Confidence Interval	() 95%; -0.071 to 0.084
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6487
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.018
	Confidence Interval	() 95%; -0.060 to 0.096
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9267
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.004
	Confidence Interval	() 95%; -0.074 to 0.081
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

33. Secondary Outcome

Title	Trough FVC Response at Week 24
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 24.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.018 (0.029)	0.038 (0.028)	0.064 (0.028)	0.001 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1603
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.056
	Confidence Interval	() 95%; -0.022 to 0.134
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0399
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.082
	Confidence Interval	() 95%; 0.004 to 0.160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6328
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.019
	Confidence Interval	() 95%; -0.059 to 0.098
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

34. Secondary Outcome

Title	Trough FVC Response at Week 32
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 32.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	0.019 (0.030)	0.080 (0.028)	0.084 (0.028)	0.077 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1270
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.061
	Confidence Interval	() 95%; -0.017 to 0.139
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1076
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.064
	Confidence Interval	() 95%; -0.014 to 0.143
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1492
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.058
	Confidence Interval	() 95%; -0.021 to 0.137
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

35. Secondary Outcome

Title	Trough FVC Response at Week 48
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 48.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	-0.061 (0.030)	0.022 (0.028)	-0.002 (0.029)	0.006 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0385
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.083
	Confidence Interval	() 95%; 0.004 to 0.162
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1420
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.059
	Confidence Interval	() 95%; -0.020 to 0.138
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0965
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.067
	Confidence Interval	() 95%; -0.012 to 0.147
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

36. Secondary Outcome

Title	Trough FVC Response at Week 40
Description	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVC performed at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug at week 40.

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	205	220	219	215
Least Squares Mean (Standard Error) [Liter]	0.028 (0.030)	0.087 (0.028)	0.086 (0.028)	0.052 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1394
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.059
	Confidence Interval	() 95%; -0.019 to 0.138
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1532
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.058
	Confidence Interval	() 95%; -0.022 to 0.137
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5511
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.024
	Confidence Interval	() 95%; -0.055 to 0.104
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Form 12 mcg minus Placebo

37. Secondary Outcome

Title	Peak FVC (0-3h) Response After 2 Weeks
Description	Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.268 (0.029)	0.454 (0.028)	0.474 (0.028)	0.551 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.186
	Confidence Interval	() 95%; 0.108 to 0.264
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.206
	Confidence Interval	() 95%; 0.128 to 0.284
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.283
	Confidence Interval	() 95%; 0.205 to 0.361
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

38. Secondary Outcome

Title	Peak FVC (0-3h) Response After 6 Weeks
Description	Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 6 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.202 (0.029)	0.411 (0.028)	0.433 (0.029)	0.467 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.209
	Confidence Interval	() 95%; 0.131 to 0.288
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.231
	Confidence Interval	() 95%; 0.153 to 0.310
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.265
	Confidence Interval	() 95%; 0.187 to 0.344
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Form 12 mcg minus Placebo

39. Secondary Outcome

Title	Peak FVC (0-3h) Response After 12 Weeks
Description	Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.194 (0.030)	0.382 (0.029)	0.432 (0.029)	0.450 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.188
	Confidence Interval	() 95%; 0.108 to 0.267
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.040
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.238
	Confidence Interval	() 95%; 0.159 to 0.318
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.256
	Confidence Interval	() 95%; 0.177 to 0.336
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Form 12 mcg minus Placebo

40. Secondary Outcome

Title	Peak FVC (0-3h) Response After 24 Weeks
Description	Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 24 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.207 (0.030)	0.379 (0.029)	0.414 (0.029)	0.424 (0.029)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.173
	Confidence Interval	() 95%; 0.092 to 0.253
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.207
	Confidence Interval	() 95%; 0.127 to 0.288
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.217
	Confidence Interval	() 95%; 0.137 to 0.298
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Form 12 mcg minus Placebo

41. Secondary Outcome

Title	Peak FVC (0-3h) Response After 48 Weeks
Description	Response was defined as change from baseline. Baseline peak FVC was defined as the mean of the available pre-dose peak FVC values prior to first dose of randomized treatment. Peak FVC (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Time Frame	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose after 48 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
Least Squares Mean (Standard Error) [Liter]	0.193 (0.031)	0.344 (0.029)	0.371 (0.030)	0.416 (0.030)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.150
	Confidence Interval	() 95%; 0.070 to 0.231
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.178
	Confidence Interval	() 95%; 0.096 to 0.259
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.041
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.223
	Confidence Interval	() 95%; 0.141 to 0.304
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.042
	Estimation Comments	Form 12 mcg minus Placebo

42. Secondary Outcome

Title	Peak Expiratory Flow Rate (PEFR) at Week 24
Description	Weekly mean pre-dose morning and evening PEFR. Results are from non-MMRM ANCOVA models by week, with Last observation carried forward (LOCF) up to each week. Fixed effects include treatment, tiotropium, strata and baseline.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	222	223	223
morning PEFR (N=214, 212, 216, 218)	196.429 (3.392)	211.496 (3.420)	211.428 (3.379)	214.070 (3.373)
evening PEFR (N=215, 211, 215, 221)	202.256 (3.363)	219.977 (3.408)	220.727 (3.360)	220.129 (3.332)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Comparison for Weekly mean morning PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	15.067
	Confidence Interval	(2-Sided) 95%; 5.962 to 24.173
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.639
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Comparison for Weekly mean morning PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.999
	Confidence Interval	() 95%; 5.949 to 24.049
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.611
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Comparison for Weekly mean morning PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.642
	Confidence Interval	(2-Sided) 95%; 8.610 to 26.673
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.601
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Comparison for Weekly mean evening PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0001
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.721
	Confidence Interval	(2-Sided) 95%; 8.680 to 26.762
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.606
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Comparison for Weekly mean evening PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	18.471
	Confidence Interval	(2-Sided) 95%; 9.484 to 27.458
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.579
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Comparison for Weekly mean evening PEFR
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.873
	Confidence Interval	(2-Sided) 95%; 8.947 to 26.799
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.548
	Estimation Comments

43. Secondary Outcome

Title	Use of Rescue Medication at Week 24
Description	Mean number of puffs of rescue medication used per day (daytime/nighttime/total)
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	217	212	216	221
Daytime	1.364 (0.097)	0.961 (0.099)	1.037 (0.097)	1.217 (0.097)
Nighttime	2.051 (0.125)	1.449 (0.126)	1.471 (0.125)	1.701 (0.124)
Total	3.390 (0.196)	2.399 (0.198)	2.488 (0.196)	2.917 (0.195)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Comparison for weekly mean daytime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0026
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.403
	Confidence Interval	(2-Sided) 95%; -0.665 to -0.141
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.133
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Comparison for weekly mean daytime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0141
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.327
	Confidence Interval	(2-Sided) 95%; -0.587 to -0.066
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.133
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Comparison for weekly mean daytime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2677
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.147
	Confidence Interval	(2-Sided) 95%; -0.406 to 0.113
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.132
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Comparison for weekly mean nighttime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0005
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.602
	Confidence Interval	(2-Sided) 95%; -0.939 to -0.266
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.171
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Comparison for weekly mean nighttime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.580
	Confidence Interval	(2-Sided) 95%; -0.914 to -0.247
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.170
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Comparison for weekly mean nighttime rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0391
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.350
	Confidence Interval	(2-Sided) 95%; -0.683 to -0.018
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.169
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Comparison for weekly mean daily (24h) rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.991
	Confidence Interval	(2-Sided) 95%; -1.518 to -0.464
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.269
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Comparison for weekly mean daily (24h) rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.902
	Confidence Interval	(2-Sided) 95%; -1.426 to -0.378
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.267
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Comparison for weekly mean daily (24h) rescue use
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0758
	Comments
	Method	ANCOVA
	Comments	non-MMRM ANCOVA models with treatment, tiotropium strata and baseline as fixed effects.
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.473
	Confidence Interval	(2-Sided) 95%; -0.994 to 0.049
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.266
	Estimation Comments

44. Secondary Outcome

Title	Patient's Global Rating (PGR) at 6 Weeks
Description	Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame	Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	194	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	3.4 (0.1)	3.0 (0.1)	3.1 (0.1)	3.1 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	() 95%; -0.6 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0073
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	() 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0017
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	() 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Form 12 mcg minus Placebo

45. Secondary Outcome

Title	Patient's Global Rating (PGR) at 12 Weeks
Description	Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	194	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	3.3 (0.1)	3.0 (0.1)	2.9 (0.1)	3.0 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0021
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	() 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	() 95%; -0.6 to -0.2
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0121
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.3
	Confidence Interval	() 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Form 12 mcg minus Placebo

46. Secondary Outcome

Title	Patient's Global Rating (PGR) at 24 Weeks
Description	Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	194	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	3.1 (0.1)	2.9 (0.1)	2.9 (0.1)	3.0 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0320
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.4 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0447
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.4 to -0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1332
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.4 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Form 12 mcg minus Placebo

47. Secondary Outcome

Title	Patient's Global Rating (PGR) at 48 Weeks
Description	Patient's Global Rating (PGR) was a patient assessment of their health (respiratory condition) at each visit (compared to the day before they started study drug) and ranged from 1 (very much better) to 7 (very much worse).
Time Frame	Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	194	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	3.1 (0.1)	3.0 (0.1)	2.9 (0.1)	2.9 (0.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4105
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.1
	Confidence Interval	() 95%; -0.3 to 0.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0584
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.4 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1006
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.2
	Confidence Interval	() 95%; -0.4 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1
	Estimation Comments	Form 12 mcg minus Placebo

48. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 6 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 6

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	0.995 (0.248)	1.566 (0.236)	1.660 (0.240)	1.753 (0.243)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0882
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.571
	Confidence Interval	() 95%; -0.085 to 1.227
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.335
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0484
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.664
	Confidence Interval	() 95%; 0.005 to 1.324
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.336
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0252
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.758
	Confidence Interval	() 95%; 0.094 to 1.421
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.338
	Estimation Comments	Form 12 mcg minus Placebo

49. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 12 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	1.412 (0.252)	1.792 (0.239)	1.955 (0.242)	1.805 (0.245)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2625
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.381
	Confidence Interval	() 95%; -0.285 to 1.047
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.340
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1109
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.543
	Confidence Interval	() 95%; -0.125 to 1.211
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.341
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2507
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.394
	Confidence Interval	() 95%; -0.278 to 1.066
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.343
	Estimation Comments	Form 12 mcg minus Placebo

50. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 18 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	1.665 (0.254)	1.897 (0.240)	2.099 (0.244)	1.689 (0.246)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4895
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.232
	Confidence Interval	() 95%; -0.439 to 0.902
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.342
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2073
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.434
	Confidence Interval	() 95%; -0.240 to 1.107
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.344
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9462
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.023
	Confidence Interval	() 95%; -0.653 to 0.700
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.345
	Estimation Comments	Form 12 mcg minus Placebo

51. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 32 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 32

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	1.732 (0.257)	1.898 (0.241)	1.698 (0.247)	1.966 (0.249)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6309
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.166
	Confidence Interval	() 95%; -0.511 to 0.842
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.345
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9227
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.034
	Confidence Interval	() 95%; -0.717 to 0.649
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.348
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5030
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.234
	Confidence Interval	() 95%; -0.451 to 0.919
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.349
	Estimation Comments	Form 12 mcg minus Placebo

52. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 40 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 40

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	1.952 (0.259)	1.839 (0.241)	1.887 (0.249)	1.575 (0.251)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7459
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.112
	Confidence Interval	() 95%; -0.793 to 0.568
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.347
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.8534
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.065
	Confidence Interval	() 95%; -0.753 to 0.623
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.351
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5099
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.377
	Confidence Interval	() 95%; -1.068 to 0.314
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.352
	Estimation Comments	Form 12 mcg minus Placebo

53. Secondary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 48 Weeks
Description	Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	192	212	207	202
Least Squares Mean (Standard Error) [score on a scale]	1.940 (0.259)	2.035 (0.242)	2.324 (0.250)	2.047 (0.251)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7850
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.095
	Confidence Interval	() 95%; -0.587 to 0.777
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.348
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2755
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.383
	Confidence Interval	() 95%; -0.306 to 1.073
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.352
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7618
	Comments
	Method	Mixed Models Analysis
	Comments	Mixed effects model with trt,tio stratum,visit,trt-by-visit as fixed effects,baseline, baseline-by-visit as fixed covariates, patient as random effect
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.107
	Confidence Interval	() 95%; -0.584 to 0.798
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.353
	Estimation Comments	Form 12 mcg minus Placebo

54. Secondary Outcome

Title	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation
Description	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.
Time Frame	Baseline to end of study at 48 weeks.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo (Tiotropium)	Placebo (Non-tiotropium)	Olo 5 mcg qd (Tiotropium)	Olo 5 mcg qd (Non-tiotropium)	Olo 10 mcg qd (Tiotropium)	Olo 10 mcg qd(Non-tiotropium)	Form 12 mcg (Tiotropium)	Form 12 mcg (Non-tiotropium)
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler - tiotropium use stratum	Matching Placebo delivered by the Respimat Inhaler - non-tiotropium use stratum.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Measure Participants	57	168	60	167	58	167	58	169
Mean (95% Confidence Interval) [Days]	143	268	136	189	134	209	223	310

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3424
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.162
	Confidence Interval	() 95%; 0.843 to 1.603
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.190
	Estimation Comments	Comparison of Olo 5 mcg qd to placebo across stratum

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olo 5 mcg qd, Olo 10 mcg qd (Tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3023
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.186
	Confidence Interval	() 95%; 0.859 to 1.636
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.195
	Estimation Comments	Comparison of Olo 10 mcg qd to placebo across stratum

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg (Tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.3589
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.854
	Confidence Interval	() 95%; 0.605 to 1.205
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.150
	Estimation Comments	Comparison of Form 12 mcg to placebo across stratum

55. Secondary Outcome

Title	Time to First Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation Leading to Hospitalization
Description	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.
Time Frame	Baseline to end of study at 48 weeks.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo (Tiotropium)	Placebo (Non-tiotropium)	Olo 5 mcg qd (Tiotropium)	Olo 5 mcg qd (Non-tiotropium)	Olo 10 mcg qd (Tiotropium)	Olo 10 mcg qd(Non-tiotropium)	Form 12 mcg (Tiotropium)	Form 12 mcg (Non-tiotropium)
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler - tiotropium use stratum	Matching Placebo delivered by the Respimat Inhaler - non-tiotropium use stratum.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Measure Participants	57	168	60	167	58	167	58	169
Mean (95% Confidence Interval) [Days]	NA	NA	NA	NA	NA	NA	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Olo 5 mcg qd, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1910
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.818
	Confidence Interval	() 95%; 0.734 to 4.503
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.841
	Estimation Comments	Comparison of Olo 5 mcg qd to placebo across stratum

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Olo 5 mcg qd, Olo 10 mcg qd(Non-tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2274
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.743
	Confidence Interval	() 95%; 0.695 to 4.369
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.817
	Estimation Comments	Comparison of Olo 10 mcg qd to placebo across stratum

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Olo 5 mcg qd, Form 12 mcg (Tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5538
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.346
	Confidence Interval	() 95%; 0.512 to 3.538
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.664
	Estimation Comments	Comparison of Form 12 mcg to placebo across stratum

56. Secondary Outcome

Title	Time to First Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbation
Description	Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.
Time Frame	Baseline to end of study at 48 weeks.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo (Tiotropium)	Placebo (Non-tiotropium)	Olo 5 mcg qd (Tiotropium)	Olo 5 mcg qd (Non-tiotropium)	Olo 10 mcg qd (Tiotropium)	Olo 10 mcg qd(Non-tiotropium)	Form 12 mcg (Tiotropium)	Form 12 mcg (Non-tiotropium)
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler - tiotropium use stratum	Matching Placebo delivered by the Respimat Inhaler - non-tiotropium use stratum.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - tiotropium stratum	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler - non-tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - tiotropium stratum	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler - non-tiotropium stratum
Measure Participants	57	168	60	167	58	167	58	169
Mean (95% Confidence Interval) [Days]	150	296	239	244	175	302	280	270

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5577
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.101
	Confidence Interval	() 95%; 0.778 to 1.557
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.195
	Estimation Comments	Comparison of Olo 5 mcg qd to placebo across stratum

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd (Tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9423
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.017
	Confidence Interval	() 95%; 0.714 to 1.448
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.184
	Estimation Comments	Comparison of Olo 10 mcg qd to placebo across stratum

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg (Tiotropium)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1097
	Comments
	Method	Log Rank
	Comments	Model included a stratification factor for tiotropium use stratum and a covariate for treatment group
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.735
	Confidence Interval	() 95%; 0.502 to 1.076
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	Estimation Comments	Comparison of Form 12 mcg to placebo across stratum

57. Secondary Outcome

Title	Number of COPD Exacerbations
Description	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 Frame	Baseline to end of study at week 48 visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	225	227	225	227
Mean (Standard Error) [Number of COPD ex. per patient year]	0.5684 (0.0718)	0.7117 (0.0793)	0.6946 (0.0801)	0.5098 (0.0649)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1729
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.2521
	Confidence Interval	() 95%; 0.9060 to 1.7304
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2064
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2297
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.2220
	Confidence Interval	() 95%; 0.8808 to 1.6954
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2039
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.5354
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	0.8968
	Confidence Interval	() 95%; 0.6353 to 1.2659
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1575
	Estimation Comments	Form 12 mcg minus Placebo

58. Secondary Outcome

Title	Number of COPD Exacerbations Requiring Hospitalization
Description	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 Frame	Baseline to end of study at week 48 visit

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	225	227	225	227
Mean (Standard Error) [Number of COPD ex. per patient year]	0.0554 (0.0249)	0.1043 (0.0378)	0.1324 (0.0493)	0.0570 (0.0227)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2508
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.8821
	Confidence Interval	() 95%; 0.6391 to 5.5430
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.0358
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1135
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	2.3877
	Confidence Interval	() 95%; 0.8122 to 7.0194
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3119
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.9611
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.0289
	Confidence Interval	() 95%; 0.3268 to 3.2395
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.6013
	Estimation Comments	Form 12 mcg minus Placebo

59. Secondary Outcome

Title	Number of Moderate Chronic Obstructive Pulmonary Disease (CPOD) Exacerbations
Description	Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.
Time Frame	Baseline to end of study at 48 weeks.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	225	227	225	227
Mean (Standard Error) [Number of COPD ex. per patient year]	0.4765 (0.0645)	0.5537 (0.0674)	0.5114 (0.0654)	0.3721 (0.0537)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.4002
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.1621
	Confidence Interval	() 95%; 0.8187 to 1.6497
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2075
	Estimation Comments	Olo 5 mcg qd minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.6983
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	1.0733
	Confidence Interval	() 95%; 0.7503 to 1.5352
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1957
	Estimation Comments	Olo 10 mcg qd minus Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2033
	Comments
	Method	Negative binomial regression
	Comments	Regression of treatment effect using tiotropium strata as a covariate, a log link function and log(exposure) as offset.
Method of Estimation	Estimation Parameter	Incidence rate ratio
	Estimated Value	0.7810
	Confidence Interval	() 95%; 0.5336 to 1.1433
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1516
	Estimation Comments	Form 12 mcg minus Placebo

60. Secondary Outcome

Title	Absolute Plasma Concentrations
Description	Absolute plasma concentrations of Olodaterol. Values presented are across visits and summarised into geometric means.
Time Frame	within 2 hours before first drug administration and 10 minutes post-dose at week 6, 12 and 18

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	0	178	205	0
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	4.179 (60.300)	7.246 (72.242)

61. Secondary Outcome

Title	Changes in Safety Parameters Related to Treatment
Description	Occurence of cardiac disorders and investigations related to treatment.
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

Treated set.

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	225	227	225	227
Tachycardia	0.4 0.2%	0.0 0%	0.0 0%	0.9 0.4%
Arrhythmia	0.0 0%	0.4 0.2%	0.0 0%	0.0 0%
Atrial fibrillation	0.4 0.2%	0.0 0%	0.0 0%	0.4 0.2%
Atrioventricular block	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Atrioventricular block first degree	0.0 0%	0.0 0%	0.0 0%	0.4 0.2%
Bundle branch block right	0.0 0%	0.4 0.2%	0.0 0%	0.0 0%
Palpitations	0.4 0.2%	0.0 0%	0.0 0%	0.4 0.2%
Ventricular extrasystoles	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Electrocardiogram QT prolonged	0.0 0%	0.4 0.2%	0.0 0%	0.4 0.2%
Electrocardiogram T wave inversion	0.0 0%	0.0 0%	0.0 0%	0.4 0.2%

62. Primary Outcome

Title	Mahler Transitional Dyspnea Index Focal Score at 24 Weeks for Combined Analysis
Description	This outcome measure describes the combined analysis of the trials NCT00793624 and NCT00796653. Mahler Transitional Dyspnea Index (TDI) focal score measures 3 components of dyspnea that evoke dyspnea in daily living: Functional Impairment, Magnitude of Task, and Magnitude of Effort. The TDI measures the change from the baseline assessment ranging from -9 (most deterioration) to +9 (most improvement).
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Placebo	Olo 5 mcg qd	Olo 10 mcg qd	Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.	Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
Measure Participants	413	433	427	417
Mean (Standard Error) [score on a scale]	1.471 (0.155)	1.980 (0.175)	1.996 (0.170)	1.827 (0.168)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 5 mcg qd
	Comments	Olo 5mcg minus placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0270
	Comments
	Method	pattern mixture model
	Comments	See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455-1497(2004)
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.509
	Confidence Interval	() 95%; 0.058 to 0.960
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.230
	Estimation Comments	Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data) 1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Olo 10 mcg qd
	Comments	Olo 10 mcg minus placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0203
	Comments	See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455-1497(2004)
	Method	pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.525
	Confidence Interval	() 95%; 0.082 to 0.967
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.226
	Estimation Comments	Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data) 1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Form 12mcg minus placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1166
	Comments
	Method	pattern mixture model
	Comments	See Hogan, et. al. Hogan JW, Roy J, Korkontzelou C Tutorial in biostatistics:handling drop-out in longitudinal studies. Stat Med 23,1455-1497(2004)
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.355
	Confidence Interval	() 95%; -0.088 to 0.799
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.226
	Estimation Comments	Based on a pattern mixture model with four patterns based on time of dropout (i.e., day of last observed data) 1) day 43 or day 85, 2) day 127 or day 169, 3) day 225 or day 281, 4) day 337

Adverse Events

Time Frame	48 weeks
Arm/Group Title	Placebo		Olodaterol (Olo) 5 mcg qd		Olodaterol (Olo) 10 mcg qd		Form 12 mcg
Arm/Group Description	Matching Placebo delivered by the Respimat Inhaler.		Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.		Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.		Foradil 12 mcg bid (morning and evening) delivered by the Aerolizer Inhaler.
All Cause Mortality
	Placebo		Olodaterol (Olo) 5 mcg qd		Olodaterol (Olo) 10 mcg qd		Form 12 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Olodaterol (Olo) 5 mcg qd		Olodaterol (Olo) 10 mcg qd		Form 12 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/225 (13.8%)		33/227 (14.5%)		26/225 (11.6%)		33/227 (14.5%)
Blood and lymphatic system disorders
Anaemia	1/225 (0.4%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Cardiac disorders
Acute coronary syndrome	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Acute myocardial infarction	1/225 (0.4%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Angina pectoris	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Atrial fibrillation	0/225 (0%)		1/227 (0.4%)		3/225 (1.3%)		1/227 (0.4%)
Bradycardia	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Cardiac failure	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		1/227 (0.4%)
Cardiac failure acute	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Cardiac failure congestive	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Cardio-respiratory arrest	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Coronary artery disease	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Coronary artery stenosis	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Hypertensive heart disease	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Myocardial infarction	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Supraventricular tachycardia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Congenital, familial and genetic disorders
Tracheo-oesophageal fistula	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Eye disorders
Iridocyclitis	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Ophthalmoplegia	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Parophthalmia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Gastrointestinal disorders
Colonic polyp	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Gastric ulcer	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Pancreatic insufficiency	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Rectal haemorrhage	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
General disorders
Chest pain	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Death	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Fatigue	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Hernia	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Mass	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Sudden death	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Hepatobiliary disorders
Bile duct stone	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Cholecystitis acute	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Jaundice	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Infections and infestations
Bronchitis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		1/227 (0.4%)
Cellulitis	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Dengue fever	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Device related infection	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Diverticulitis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Gastroenteritis	3/225 (1.3%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Infective exacerbation of chronic obstructive airways disease	2/225 (0.9%)		0/227 (0%)		1/225 (0.4%)		1/227 (0.4%)
Meningitis	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Pneumonia	3/225 (1.3%)		6/227 (2.6%)		8/225 (3.6%)		3/227 (1.3%)
Respiratory tract infection	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Sepsis	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Septic shock	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Sinusitis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Upper respiratory tract infection	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Urinary tract infection	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Wound abscess	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Injury, poisoning and procedural complications
Fall	1/225 (0.4%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Femur fracture	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Foreign body	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Humerus fracture	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Incisional hernia	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Joint dislocation	0/225 (0%)		1/227 (0.4%)		1/225 (0.4%)		0/227 (0%)
Ligament sprain	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Lower limb fracture	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Muscle strain	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Overdose	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Road traffic accident	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Tendon rupture	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Investigations
Blood pressure decreased	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Electrocardiogram QT prolonged	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Electrocardiogram T wave inversion	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/225 (0.4%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Hyperkalaemia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Hypoglycaemia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Myositis	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Osteoarthritis	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Pathological fracture	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Diffuse large B-cell lymphoma	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Gastric neoplasm	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Lung adenocarcinoma	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		1/227 (0.4%)
Lung neoplasm malignant	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		1/227 (0.4%)
Lung squamous cell carcinoma stage unspecified	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Oesophageal squamous cell carcinoma	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Prostate cancer	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		1/227 (0.4%)
Squamous cell carcinoma	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Thyroid neoplasm	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Nervous system disorders
Cerebral infarction	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Cerebrovascular accident	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Complex regional pain syndrome	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Dizziness	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Paraesthesia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Psychiatric disorders
Completed suicide	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Renal and urinary disorders
Acute prerenal failure	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Azotaemia	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Haematuria	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Nephrolithiasis	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Renal failure	1/225 (0.4%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Renal failure acute	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/225 (0.4%)		1/227 (0.4%)		1/225 (0.4%)		1/227 (0.4%)
Chronic obstructive pulmonary disease	9/225 (4%)		10/227 (4.4%)		13/225 (5.8%)		9/227 (4%)
Haemoptysis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Hypoxia	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Lung infiltration	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Pneumothorax	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Pulmonary embolism	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Respiratory failure	2/225 (0.9%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Surgical and medical procedures
Dental care	0/225 (0%)		1/227 (0.4%)		0/225 (0%)		0/227 (0%)
Vascular disorders
Aortic aneurysm rupture	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Arteriosclerosis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Deep vein thrombosis	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Hypertension	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		0/227 (0%)
Hypovolaemic shock	1/225 (0.4%)		0/227 (0%)		0/225 (0%)		0/227 (0%)
Intermittent claudication	0/225 (0%)		0/227 (0%)		1/225 (0.4%)		1/227 (0.4%)
Peripheral arterial occlusive disease	0/225 (0%)		0/227 (0%)		0/225 (0%)		1/227 (0.4%)
Other (Not Including Serious) Adverse Events
	Placebo		Olodaterol (Olo) 5 mcg qd		Olodaterol (Olo) 10 mcg qd		Form 12 mcg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	83/225 (36.9%)		100/227 (44.1%)		96/225 (42.7%)		83/227 (36.6%)
Infections and infestations
Nasopharyngitis	15/225 (6.7%)		22/227 (9.7%)		25/225 (11.1%)		23/227 (10.1%)
Upper respiratory tract infection	15/225 (6.7%)		17/227 (7.5%)		11/225 (4.9%)		11/227 (4.8%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	51/225 (22.7%)		67/227 (29.5%)		62/225 (27.6%)		53/227 (23.3%)
Cough	7/225 (3.1%)		7/227 (3.1%)		13/225 (5.8%)		13/227 (5.7%)
Dyspnoea	11/225 (4.9%)		9/227 (4%)		13/225 (5.8%)		6/227 (2.6%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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