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

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00796653
• Collaborator: (none)
• Enrollment: 937
• Locations: 98
• Arms: 4
• Patients Per Site: 9.6

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	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 937 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: Jan 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 devices for comparison with Olodaterol (BI 1744) on 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 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).

3. 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).

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 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.

33. 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.

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

    Occurence of cardiac disorders and investigations related to treatment.

58. Absolute Plasma Concentrations [within 2 hours before first study 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.

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	1222.14.5004 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
2	1222.14.5005 Boehringer Ingelheim Investigational Site	Florencio Varela		Argentina
3	1222.14.5003 Boehringer Ingelheim Investigational Site	Mar del Plata		Argentina
4	1222.14.5001 Boehringer Ingelheim Investigational Site	Mendoza		Argentina
5	1222.14.5002 Boehringer Ingelheim Investigational Site	Quilmes		Argentina
6	1222.14.5106 Boehringer Ingelheim Investigational Site	Florianopolis		Brazil
7	1222.14.5101 Boehringer Ingelheim Investigational Site	Porto Alegre		Brazil
8	1222.14.5103 Boehringer Ingelheim Investigational Site	Porto Alegre		Brazil
9	1222.14.5104 Boehringer Ingelheim Investigational Site	Porto Alegre		Brazil
10	1222.14.5102 Boehringer Ingelheim Investigational Site	Recife		Brazil
11	1222.14.5105 Boehringer Ingelheim Investigational Site	Sao Paulo		Brazil
12	1222.14.4005 Boehringer Ingelheim Investigational Site	Calgary	Alberta	Canada
13	1222.14.4002 Boehringer Ingelheim Investigational Site	Kelowna	British Columbia	Canada
14	1222.14.4004 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia	Canada
15	1222.14.4009 Boehringer Ingelheim Investigational Site	Moncton	New Brunswick	Canada
16	1222.14.4010 Boehringer Ingelheim Investigational Site	St. John's	Newfoundland and Labrador	Canada
17	1222.14.4008 Boehringer Ingelheim Investigational Site	Grimsby	Ontario	Canada
18	1222.14.4014 Boehringer Ingelheim Investigational Site	Mississauga	Ontario	Canada
19	1222.14.4007 Boehringer Ingelheim Investigational Site	Newmarket	Ontario	Canada
20	1222.14.4013 Boehringer Ingelheim Investigational Site	Ottawa	Ontario	Canada
21	1222.14.4001 Boehringer Ingelheim Investigational Site	Scarborough	Ontario	Canada
22	1222.14.4012 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
23	1222.14.4015 Boehringer Ingelheim Investigational Site	Sherbrooke	Quebec	Canada
24	1222.14.4011 Boehringer Ingelheim Investigational Site	Saskatoon	Saskatchewan	Canada
25	1222.14.4006 Boehringer Ingelheim Investigational Site	Quebec		Canada
26	1222.14.6004 Boehringer Ingelheim Investigational Site	Brno		Czech Republic
27	1222.14.6003 Boehringer Ingelheim Investigational Site	Hradec Kralove		Czech Republic
28	1222.14.6002 Boehringer Ingelheim Investigational Site	Kyjov		Czech Republic
29	1222.14.6001 Boehringer Ingelheim Investigational Site	Znojmo		Czech Republic
30	1222.14.4602 Boehringer Ingelheim Investigational Site	Helsingør		Denmark
31	1222.14.4601 Boehringer Ingelheim Investigational Site	Hillerød		Denmark
32	1222.14.4603 Boehringer Ingelheim Investigational Site	Roskilde		Denmark
33	1222.14.4702 Boehringer Ingelheim Investigational Site	Espoo		Finland
34	1222.14.4701 Boehringer Ingelheim Investigational Site	HUS		Finland
35	1222.14.4703 Boehringer Ingelheim Investigational Site	Lohja		Finland
36	1222.14.4106 Boehringer Ingelheim Investigational Site	Aschaffenburg		Germany
37	1222.14.4112 Boehringer Ingelheim Investigational Site	Berlin		Germany
38	1222.14.4103 Boehringer Ingelheim Investigational Site	Frankfurt		Germany
39	1222.14.4110 Boehringer Ingelheim Investigational Site	Frankfurt		Germany
40	1222.14.4108 Boehringer Ingelheim Investigational Site	Gelnhausen		Germany
41	1222.14.4107 Boehringer Ingelheim Investigational Site	Kelkheim		Germany
42	1222.14.4114 Boehringer Ingelheim Investigational Site	Lübeck		Germany
43	1222.14.4111 Boehringer Ingelheim Investigational Site	Mainz		Germany
44	1222.14.4113 Boehringer Ingelheim Investigational Site	Minden		Germany
45	1222.14.4109 Boehringer Ingelheim Investigational Site	Mönchengladbach		Germany
46	1222.14.4104 Boehringer Ingelheim Investigational Site	Rodgau-Dudenhofen		Germany
47	1222.14.4105 Boehringer Ingelheim Investigational Site	Wiesloch		Germany
48	1222.14.5501 Boehringer Ingelheim Investigational Site	Hong Kong		Hong Kong
49	1222.14.5412 Boehringer Ingelheim Investigational Site	Coimbatore		India
50	1222.14.5406 Boehringer Ingelheim Investigational Site	Hyderabad		India
51	1222.14.5402 Boehringer Ingelheim Investigational Site	Indore		India
52	1222.14.5405 Boehringer Ingelheim Investigational Site	Jaipur		India
53	1222.14.5409 Boehringer Ingelheim Investigational Site	Jaipur		India
54	1222.14.5403 Boehringer Ingelheim Investigational Site	Mangalore		India
55	1222.14.5407 Boehringer Ingelheim Investigational Site	Mysore		India
56	1222.14.5404 Boehringer Ingelheim Investigational Site	Nagpur		India
57	1222.14.5408 Boehringer Ingelheim Investigational Site	Noida		India
58	1222.14.5401 Boehringer Ingelheim Investigational Site	Pune		India
59	1222.14.5410 Boehringer Ingelheim Investigational Site	Vellore		India
60	1222.14.4301 Boehringer Ingelheim Investigational Site	Cassano Delle Murge (ba)		Italy
61	1222.14.4302 Boehringer Ingelheim Investigational Site	Genova		Italy
62	1222.14.4304 Boehringer Ingelheim Investigational Site	Milano		Italy
63	1222.14.4305 Boehringer Ingelheim Investigational Site	Parma		Italy
64	1222.14.4303 Boehringer Ingelheim Investigational Site	Roma		Italy
65	1222.14.5301 Boehringer Ingelheim Investigational Site	Bucheon		Korea, Republic of
66	1222.14.5302 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
67	1222.14.5305 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
68	1222.14.5306 Boehringer Ingelheim Investigational Site	Seoul		Korea, Republic of
69	1222.14.5304 Boehringer Ingelheim Investigational Site	Uijeongbu		Korea, Republic of
70	1222.14.5303 Boehringer Ingelheim Investigational Site	Wonju		Korea, Republic of
71	1222.14.5701 Boehringer Ingelheim Investigational Site	Georgetown, Pulau Pinang		Malaysia
72	1222.14.5703 Boehringer Ingelheim Investigational Site	Kuala Lumpur		Malaysia
73	1222.14.5702 Boehringer Ingelheim Investigational Site	Kuching, Sarawak		Malaysia
74	1222.14.4802 Boehringer Ingelheim Investigational Site	Fredrikstad		Norway
75	1222.14.4801 Boehringer Ingelheim Investigational Site	SKI		Norway
76	1222.14.5802 Boehringer Ingelheim Investigational Site	Iloilo City		Philippines
77	1222.14.5803 Boehringer Ingelheim Investigational Site	Iloilo City		Philippines
78	1222.14.5801 Boehringer Ingelheim Investigational Site	Manila		Philippines
79	1222.14.6103 Boehringer Ingelheim Investigational Site	Brasov		Romania
80	1222.14.6102 Boehringer Ingelheim Investigational Site	Constanta		Romania
81	1222.14.6101 Boehringer Ingelheim Investigational Site	Iasi		Romania
82	1222.14.6203 Boehringer Ingelheim Investigational Site	Petrozavodsk		Russian Federation
83	1222.14.6201 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
84	1222.14.6202 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
85	1222.14.4901 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
86	1222.14.4902 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
87	1222.14.4401 Boehringer Ingelheim Investigational Site	Barcelona		Spain
88	1222.14.4402 Boehringer Ingelheim Investigational Site	Barcelona		Spain
89	1222.14.4406 Boehringer Ingelheim Investigational Site	Madrid		Spain
90	1222.14.4405 Boehringer Ingelheim Investigational Site	Mérida		Spain
91	1222.14.4403 Boehringer Ingelheim Investigational Site	Palma de Mallorca		Spain
92	1222.14.4407 Boehringer Ingelheim Investigational Site	Terrassa (Barcelona)		Spain
93	1222.14.4501 Boehringer Ingelheim Investigational Site	Boden		Sweden
94	1222.14.4503 Boehringer Ingelheim Investigational Site	Göteboerg		Sweden
95	1222.14.4502 Boehringer Ingelheim Investigational Site	Lund		Sweden
96	1222.14.5904 Boehringer Ingelheim Investigational Site	Bangkok		Thailand
97	1222.14.5901 Boehringer Ingelheim Investigational Site	Khon Kaen		Thailand
98	1222.14.5902 Boehringer Ingelheim Investigational Site	Songkla		Thailand

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: NCT00796653
• Other Study ID Numbers: 1222.14; 2008-001934-28
• First Posted: Nov 24, 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	Three patients were randomized but not treated due to withdrawn consent and findings on pre-dose ECG prior to receiving study medication.

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	235	232	234	233
COMPLETED	184	195	198	193
NOT COMPLETED	51	37	36	40

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	235	232	234	233	934
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.9 (7.8)	63.7 (8.8)	63.8 (8.5)	65.0 (8.2)	64.183 (8.7)
Sex: Female, Male (Count of Participants)
Female	40 17%	45 19.4%	50 21.4%	41 17.6%	176 18.8%
Male	195 83%	187 80.6%	184 78.6%	192 82.4%	758 81.2%
Tiotropium (Tio) Use Stratum (Number of participants) [Number]
Non-tiotropium	173 73.6%	174 75%	172 73.5%	174 74.7%	693 74.2%
Tiotropium	62 26.4%	58 25%	62 26.5%	59 25.3%	241 25.8%

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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	-0.013 (0.014)	0.116 (0.014)	0.140 (0.014)	0.137 (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	0.129
	Confidence Interval	() 95%; 0.091 to 0.167
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.154
	Confidence Interval	() 95%; 0.116 to 0.191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.150
	Confidence Interval	() 95%; 0.112 to 0.188
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.055 (0.014)	-0.003 (0.014)	0.014 (0.014)	-0.013 (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	0.0055
	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	0.053
	Confidence Interval	() 95%; 0.015 to 0.090
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0003
	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	0.069
	Confidence Interval	() 95%; 0.032 to 0.106
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0270
	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%; 0.005 to 0.080
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.102 (0.229)	1.504 (0.225)	1.521 (0.225)	1.703 (0.228)

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	0.1999
	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	0.402
	Confidence Interval	() 95%; -0.213 to 1.018
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.314
	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	0.1818
	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	0.419
	Confidence Interval	() 95%; -0.196 to 1.035
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.314
	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	0.0572
	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	0.602
	Confidence Interval	() 95%; -0.019 to 1.222
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.316
	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	202	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	42.120 (0.995)	38.970 (0.965)	38.597 (0.969)	40.704 (0.984)

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	0.0197
	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	-3.150
	Confidence Interval	() 95%; -5.796 to -0.503
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.349
	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	0.0094
	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	-3.524
	Confidence Interval	() 95%; -6.180 to -0.867
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.354
	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	0.2995
	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	-1.416
	Confidence Interval	() 95%; -4.093 to 1.261
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.365
	Estimation Comments	Form 12 mcg minus Placebo

5. 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	202	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	39.914 (1.022)	39.562 (0.986)	38.824 (0.991)	40.025 (0.996)

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	0.7995
	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	-0.352
	Confidence Interval	() 95%; -3.068 to 2.365
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.385
	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	0.4336
	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	-1.090
	Confidence Interval	() 95%; -3.818 to 1.639
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.391
	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	0.9365
	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	0.111
	Confidence Interval	() 95%; -2.625 to 2.848
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.395
	Estimation Comments	Form 12 mcg minus Placebo

6. 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	202	216	212	206
Least Squares Mean (Standard Error) [score on a scale]	42.679 (0.983)	40.054 (0.955)	40.190 (0.963)	39.521 (0.975)

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	0.0491
	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	-2.625
	Confidence Interval	() 95%; -5.241 to -0.010
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.333
	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	0.0636
	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	-2.489
	Confidence Interval	() 95%; -5.119 to 0.141
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.341
	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	0.0194
	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	-3.158
	Confidence Interval	() 95%; -5.806 to -0.511
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.350
	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
Least Squares 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 minus placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0034
	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	-2.846
	Confidence Interval	(2-Sided) 95%; -4.751 to -0.940
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.972
	Estimation Comments

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	0.0004
	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	-3.434
	Confidence Interval	(2-Sided) 95%; -5.343 to -1.525
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.973
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Form 12 mcg
	Comments	Form 12 mcg minus placebo
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.2009
	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	-1.248
	Confidence Interval	(2-Sided) 95%; -3.161 to 0.665
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.976
	Estimation Comments

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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.021 (0.013)	0.181 (0.014)	0.214 (0.013)	0.183 (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	0.160
	Confidence Interval	() 95%; 0.123 to 0.196
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.193
	Confidence Interval	() 95%; 0.157 to 0.229
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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%; 0.126 to 0.199
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	-0.010 (0.014)	0.162 (0.014)	0.181 (0.014)	0.174 (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	0.172
	Confidence Interval	() 95%; 0.136 to 0.209
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.192
	Confidence Interval	() 95%; 0.155 to 0.228
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.184
	Confidence Interval	() 95%; 0.148 to 0.221
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	-0.008 (0.014)	0.138 (0.014)	0.167 (0.014)	0.163 (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	0.145
	Confidence Interval	() 95%; 0.108 to 0.182
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.175
	Confidence Interval	() 95%; 0.138 to 0.212
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.170
	Confidence Interval	() 95%; 0.133 to 0.208
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	-0.025 (0.014)	0.093 (0.014)	0.116 (0.014)	0.104 (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	0.118
	Confidence Interval	() 95%; 0.080 to 0.156
	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	0.141
	Confidence Interval	() 95%; 0.103 to 0.180
	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	0.129
	Confidence Interval	() 95%; 0.091 to 0.168
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.016 (0.013)	0.053 (0.013)	0.103 (0.013)	0.033 (0.013)

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	0.069
	Confidence Interval	() 95%; 0.033 to 0.105
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	0.119
	Confidence Interval	() 95%; 0.083 to 0.155
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	0.0071
	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%; 0.013 to 0.085
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.036 (0.013)	0.047 (0.013)	0.068 (0.013)	0.034 (0.013)

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	0.084
	Confidence Interval	() 95%; 0.048 to 0.120
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	0.104
	Confidence Interval	() 95%; 0.068 to 0.141
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	0.070
	Confidence Interval	() 95%; 0.034 to 0.106
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.018
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.041 (0.014)	0.018 (0.013)	0.052 (0.013)	0.024 (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	0.0017
	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%; 0.022 to 0.095
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.093
	Confidence Interval	() 95%; 0.057 to 0.130
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.065
	Confidence Interval	() 95%; 0.028 to 0.101
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.036 (0.014)	0.013 (0.014)	0.049 (0.013)	0.015 (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	0.0085
	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	0.050
	Confidence Interval	() 95%; 0.013 to 0.087
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.086
	Confidence Interval	() 95%; 0.049 to 0.122
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0067
	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	0.051
	Confidence Interval	() 95%; 0.014 to 0.088
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.039 (0.014)	0.023 (0.014)	0.034 (0.014)	0.009 (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	0.0012
	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	0.062
	Confidence Interval	() 95%; 0.025 to 0.100
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.073
	Confidence Interval	() 95%; 0.035 to 0.110
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0117
	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	0.048
	Confidence Interval	() 95%; 0.011 to 0.086
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.043 (0.014)	0.019 (0.014)	0.041 (0.014)	0.013 (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	0.0014
	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	0.062
	Confidence Interval	() 95%; 0.024 to 0.099
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.084
	Confidence Interval	() 95%; 0.047 to 0.122
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0035
	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%; 0.019 to 0.094
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.060 (0.014)	-0.016 (0.014)	-0.001 (0.014)	-0.024 (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	0.0228
	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%; 0.006 to 0.082
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0024
	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%; 0.021 to 0.097
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.0664
	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	0.036
	Confidence Interval	() 95%; -0.002 to 0.074
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.099 (0.014)	0.260 (0.014)	0.278 (0.014)	0.253 (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	0.161
	Confidence Interval	() 95%; 0.122 to 0.199
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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%; 0.140 to 0.216
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	0.153
	Confidence Interval	() 95%; 0.115 to 0.191
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.019
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.066 (0.014)	0.235 (0.014)	0.248 (0.014)	0.242 (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	0.168
	Confidence Interval	() 95%; 0.130 to 0.207
	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	0.181
	Confidence Interval	() 95%; 0.143 to 0.220
	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	0.176
	Confidence Interval	() 95%; 0.137 to 0.214
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.064 (0.014)	0.206 (0.014)	0.232 (0.014)	0.228 (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	0.141
	Confidence Interval	() 95%; 0.103 to 0.180
	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	0.168
	Confidence Interval	() 95%; 0.129 to 0.207
	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	0.164
	Confidence Interval	() 95%; 0.125 to 0.203
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.060 (0.015)	0.183 (0.014)	0.211 (0.014)	0.203 (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	0.123
	Confidence Interval	() 95%; 0.084 to 0.163
	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	0.151
	Confidence Interval	() 95%; 0.112 to 0.191
	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	0.143
	Confidence Interval	() 95%; 0.104 to 0.183
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.052 (0.015)	0.163 (0.015)	0.178 (0.015)	0.170 (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	0.112
	Confidence Interval	() 95%; 0.071 to 0.152
	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	0.126
	Confidence Interval	() 95%; 0.086 to 0.166
	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	0.118
	Confidence Interval	() 95%; 0.078 to 0.158
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.020
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.082 (0.025)	0.312 (0.025)	0.332 (0.025)	0.348 (0.025)

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	0.231
	Confidence Interval	() 95%; 0.162 to 0.299
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.250
	Confidence Interval	() 95%; 0.182 to 0.318
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.266
	Confidence Interval	() 95%; 0.198 to 0.334
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.027 (0.025)	0.277 (0.026)	0.276 (0.025)	0.307 (0.026)

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	0.251
	Confidence Interval	() 95%; 0.182 to 0.320
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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%; 0.180 to 0.318
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.281
	Confidence Interval	() 95%; 0.212 to 0.350
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.006 (0.026)	0.235 (0.026)	0.253 (0.026)	0.280 (0.026)

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	0.229
	Confidence Interval	() 95%; 0.159 to 0.299
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.247
	Confidence Interval	() 95%; 0.177 to 0.317
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.275
	Confidence Interval	() 95%; 0.205 to 0.345
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.012 (0.026)	0.212 (0.026)	0.225 (0.026)	0.253 (0.026)

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	0.199
	Confidence Interval	() 95%; 0.128 to 0.270
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.213
	Confidence Interval	() 95%; 0.142 to 0.283
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.241
	Confidence Interval	() 95%; 0.170 to 0.312
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	-0.036 (0.027)	0.182 (0.026)	0.201 (0.026)	0.184 (0.026)

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	0.218
	Confidence Interval	() 95%; 0.146 to 0.290
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.237
	Confidence Interval	() 95%; 0.166 to 0.309
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.220
	Confidence Interval	() 95%; 0.148 to 0.292
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	0.030 (0.026)	0.118 (0.026)	0.173 (0.026)	0.111 (0.026)

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	0.0133
	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	0.088
	Confidence Interval	() 95%; 0.018 to 0.157
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.143
	Confidence Interval	() 95%; 0.073 to 0.212
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	0.0212
	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%; 0.012 to 0.151
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.035
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.014 (0.026)	0.113 (0.026)	0.101 (0.026)	0.085 (0.026)

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	0.0004
	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	0.127
	Confidence Interval	() 95%; 0.057 to 0.197
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.0012
	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	0.115
	Confidence Interval	() 95%; 0.045 to 0.185
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.0056
	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	0.099
	Confidence Interval	() 95%; 0.029 to 0.169
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.041 (0.026)	0.062 (0.026)	0.062 (0.026)	0.070 (0.026)

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	0.0045
	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	0.103
	Confidence Interval	() 95%; 0.032 to 0.173
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.0046
	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	0.102
	Confidence Interval	() 95%; 0.032 to 0.173
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.0023
	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%; 0.039 to 0.181
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.014 (0.027)	0.084 (0.026)	0.107 (0.026)	0.064 (0.026)

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	0.0077
	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%; 0.026 to 0.169
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.0009
	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	0.121
	Confidence Interval	() 95%; 0.050 to 0.193
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.036
	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	0.078
	Confidence Interval	() 95%; 0.006 to 0.149
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.044 (0.027)	0.023 (0.026)	0.019 (0.026)	-0.005 (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	0.0718
	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	0.066
	Confidence Interval	() 95%; -0.006 to 0.139
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.0863
	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	0.063
	Confidence Interval	() 95%; -0.009 to 0.135
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.2982
	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	0.038
	Confidence Interval	() 95%; -0.034 to 0.111
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.007 (0.027)	0.081 (0.027)	0.063 (0.027)	0.036 (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	0.0190
	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%; 0.014 to 0.160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.0601
	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	0.070
	Confidence Interval	() 95%; -0.003 to 0.143
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.2573
	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%; -0.031 to 0.115
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	Estimation Comments	Form 12 mcg minus Placebo

35. 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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.016 (0.027)	0.071 (0.027)	0.105 (0.027)	0.037 (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	0.0200
	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%; 0.014 to 0.160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.0013
	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	0.121
	Confidence Interval	() 95%; 0.047 to 0.194
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.1598
	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	0.053
	Confidence Interval	() 95%; -0.021 to 0.126
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	Estimation Comments	Form 12 mcg minus Placebo

36. 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	232	229	228	229
Least Squares Mean (Standard Error) [Liter]	-0.069 (0.027)	0.012 (0.027)	0.032 (0.027)	-0.031 (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	0.0307
	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	0.081
	Confidence Interval	() 95%; 0.008 to 0.155
	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	0.0073
	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	0.101
	Confidence Interval	() 95%; 0.027 to 0.175
	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	0.3147
	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	0.038
	Confidence Interval	() 95%; -0.036 to 0.112
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.247 (0.027)	0.480 (0.027)	0.476 (0.027)	0.495 (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	0.233
	Confidence Interval	() 95%; 0.160 to 0.306
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.229
	Confidence Interval	() 95%; 0.156 to 0.302
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.248
	Confidence Interval	() 95%; 0.175 to 0.321
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.196 (0.027)	0.443 (0.027)	0.417 (0.027)	0.450 (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	0.247
	Confidence Interval	() 95%; 0.174 to 0.321
	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	0.221
	Confidence Interval	() 95%; 0.148 to 0.295
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.037
	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	0.254
	Confidence Interval	() 95%; 0.180 to 0.328
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.171 (0.028)	0.386 (0.027)	0.396 (0.027)	0.436 (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	0.215
	Confidence Interval	() 95%; 0.141 to 0.289
	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	0.226
	Confidence Interval	() 95%; 0.151 to 0.300
	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	0.265
	Confidence Interval	() 95%; 0.191 to 0.340
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.038
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.189 (0.028)	0.371 (0.028)	0.369 (0.028)	0.397 (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%; 0.106 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	0.180
	Confidence Interval	() 95%; 0.105 to 0.256
	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	0.207
	Confidence Interval	() 95%; 0.132 to 0.283
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	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	233	230	233	232
Least Squares Mean (Standard Error) [Liter]	0.137 (0.029)	0.325 (0.028)	0.352 (0.028)	0.329 (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	0.188
	Confidence Interval	() 95%; 0.111 to 0.265
	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	0.214
	Confidence Interval	() 95%; 0.138 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	0.192
	Confidence Interval	() 95%; 0.115 to 0.269
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.039
	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	233	230	233	232
morning PEFR (N=225, 227, 226, 224)	196.789 (3.270)	210.496 (3.253)	217.660 (3.274)	211.038 (3.299)
evening PEFR (N=224, 223, 227, 222)	202.505 (3.281)	219.905 (3.289)	225.380 (3.281)	218.321 (3.321)

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	0.0021
	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	13.707
	Confidence Interval	(2-Sided) 95%; 5.004 to 22.411
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.435
	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	<0.0001
	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	20.871
	Confidence Interval	(2-Sided) 95%; 12.158 to 29.584
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.440
	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	0.0014
	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	14.249
	Confidence Interval	(2-Sided) 95%; 5.506 to 22.991
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.454
	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	0.0001
	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	17.400
	Confidence Interval	(2-Sided) 95%; 8.640 to 26.160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.463
	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	<0.0001
	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	22.875
	Confidence Interval	(2-Sided) 95%; 14.153 to 31.596
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.444
	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	0.0004
	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	15.816
	Confidence Interval	(2-Sided) 95%; 7.032 to 24.599
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 4.475
	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	227	228	229	224
Daytime	1.189 (0.089)	1.036 (0.089)	0.923 (0.089)	0.967 (0.090)
Nighttime	1.713 (0.112)	1.435 (0.111)	1.348 (0.112)	1.393 (0.113)
Total	2.893 (0.187)	2.470 (0.187)	2.277 (0.188)	2.353 (0.190)

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	0.2057
	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	-0.153
	Confidence Interval	(2-Sided) 95%; -0.391 to -0.084
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.121
	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	0.0284
	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	-0.266
	Confidence Interval	(2-Sided) 95%; -0.504 to -0.028
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.121
	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	0.0685
	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	-0.222
	Confidence Interval	(2-Sided) 95%; -0.461 to 0.017
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.122
	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	0.0674
	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	-0.278
	Confidence Interval	(2-Sided) 95%; -0.576 to 0.020
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.152
	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	0.0163
	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	-0.365
	Confidence Interval	(2-Sided) 95%; -0.662 to -0.067
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.0163
	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	0.0364
	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	-0.320
	Confidence Interval	(2-Sided) 95%; -0.620 to -0.020
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.153
	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	0.0959
	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	-0.424
	Confidence Interval	(2-Sided) 95%; -0.922 to 0.075
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.254
	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	0.0155
	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	-0.616
	Confidence Interval	(2-Sided) 95%; -1.115 to -0.117
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.254
	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	0.0347
	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	-0.541
	Confidence Interval	(2-Sided) 95%; -1.042 to -0.039
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.256
	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	224	225	225	221
Least Squares Mean (Standard Error) [score on a scale]	3.4 (0.1)	3.1 (0.1)	3.2 (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	0.0164
	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	0.0196
	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	0.0041
	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	224	225	225	221
Least Squares Mean (Standard Error) [score on a scale]	3.3 (0.1)	3.1 (0.1)	3.0 (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	0.0388
	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	0.0038
	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	0.0053
	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	224	225	225	221
Least Squares Mean (Standard Error) [score on a scale]	3.3 (0.1)	3.1 (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	0.0555
	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	0.0122
	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 -0.1
	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	0.0144
	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 -0.1
	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	224	225	225	221
Least Squares Mean (Standard Error) [score on a scale]	3.2 (0.1)	3.2 (0.1)	3.0 (0.1)	3.2 (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	0.5707
	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	0.0814
	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	0.7413
	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	-0.0
	Confidence Interval	() 95%; -0.2 to 0.2
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	0.980 (0.221)	1.417 (0.221)	1.686 (0.222)	1.444 (0.224)

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	0.1524
	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	0.437
	Confidence Interval	() 95%; -0.162 to 1.036
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.305
	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	0.0211
	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	0.706
	Confidence Interval	() 95%; 0.106 to 1.307
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.306
	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	0.1314
	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	0.464
	Confidence Interval	() 95%; -0.139 to 1.066
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.307
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.080 (0.224)	1.742 (0.222)	1.747 (0.224)	1.499 (0.226)

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	0.0319
	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	0.662
	Confidence Interval	() 95%; 0.057 to 1.267
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.308
	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	0.0312
	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	0.667
	Confidence Interval	() 95%; 0.060 to 1.274
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.310
	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	0.1777
	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	0.419
	Confidence Interval	() 95%; -0.191 to 1.029
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.311
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.0454 (0.227)	1.470 (0.223)	1.537 (0.224)	1.579 (0.227)

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	0.1714
	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	0.425
	Confidence Interval	() 95%; -0.184 to 1.035
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.311
	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	0.1142
	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	0.492
	Confidence Interval	() 95%; -0.119 to 1.103
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.312
	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	0.0888
	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	0.534
	Confidence Interval	() 95%; -0.081 to 1.150
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.314
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.168 (0.232)	1.658 (0.228)	1.522 (0.228)	1.477 (0.229)

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	0.1235
	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	0.490
	Confidence Interval	() 95%; -0.134 to 1.113
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.318
	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	0.2666
	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	0.354
	Confidence Interval	() 95%; -0.271 to 0.978
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.318
	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	0.3335
	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	0.309
	Confidence Interval	() 95%; -0.317 to 0.934
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.319
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.064 (0.234)	1.377 (0.229)	1.545 (0.229)	1.178 (0.231)

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	0.3287
	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	0.313
	Confidence Interval	() 95%; -0.315 to 0.941
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.320
	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	0.1341
	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	0.481
	Confidence Interval	() 95%; -0.148 to 1.109
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.321
	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	0.7220
	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	0.114
	Confidence Interval	() 95%; -0.516 to 0.745
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.322
	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	221	221	220	215
Least Squares Mean (Standard Error) [score on a scale]	1.113 (0.234)	1.510 (0.231)	1.831 (0.230)	1.280 (0.232)

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	0.2176
	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	0.397
	Confidence Interval	() 95%; -0.234 to 1.027
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.322
	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	0.0258
	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	0.718
	Confidence Interval	() 95%; 0.087 to 1.348
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.323
	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	0.6044
	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%; -0.466 to 0.800
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.323
	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

[Not Specified]

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	61	174	59	173	59	175	58	175
Mean (95% Confidence Interval) [Days]	173	177	252	270	252	234	149	232

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	0.1946
	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	0.802
	Confidence Interval	() 95%; 0.580 to 1.111
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.133
	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	0.4071
	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	0.872
	Confidence Interval	() 95%; 0.634 to 1.198
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.141
	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	0.6404
	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	0.922
	Confidence Interval	() 95%; 0.670 to 1.267
	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

[Not Specified]

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	61	174	59	173	59	175	58	175
Mean (95% Confidence Interval) [Days]	NA	NA	NA	NA	NA	NA	NA	368.0

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	0.2942
	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	0.685
	Confidence Interval	() 95%; 0.336 to 1.399
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.249
	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	0.8594
	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	0.947
	Confidence Interval	() 95%; 0.493 to 1.820
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.316
	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	0.5466
	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	0.803
	Confidence Interval	() 95%; 0.405 to 1.593
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.281
	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

[Not Specified]

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	61	174	59	173	59	175	58	175
Mean (95% Confidence Interval) [Days]	176	214	264	312	324	327	190	325

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	0.2494
	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	0.807
	Confidence Interval	() 95%; 0.566 to 1.150
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.146
	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	0.2006
	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	0.791
	Confidence Interval	() 95%; 0.555 to 1.126
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.143
	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	0.5795
	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	0.903
	Confidence Interval	() 95%; 0.637 to 1.279
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.160
	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	235	232	234	233
Mean (Standard Error) [Number of COPD ex. per patient year]	0.6890 (0.0829)	0.5409 (0.0690)	0.5947 (0.0736)	0.7325 (0.0861)

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	0.1571
	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	0.7850
	Confidence Interval	() 95%; 0.5613 to 1.0979
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1342
	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	0.3814
	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	0.8631
	Confidence Interval	() 95%; 0.6205 to 1.2005
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1451
	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	0.7098
	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	1.0631
	Confidence Interval	() 95%; 0.7699 to 1.4680
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1748
	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	235	232	234	233
Mean (Standard Error) [Number of COPD ex. per patient year]	0.0986 (0.0258)	0.0781 (0.0221)	0.0993 (0.0253)	0.1025 (0.0262)

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	0.5326
	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	0.7925
	Confidence Interval	() 95%; 0.3814 to 1.6464
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.2952
	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	0.9824
	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	1.0078
	Confidence Interval	() 95%; 0.5038 to 2.0160
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3560
	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	0.9112
	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	1.0403
	Confidence Interval	() 95%; 0.5194 to 2.0832
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.3681
	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	235	232	234	233
Mean (Standard Error) [Number of COPD ex. per patient year]	0.5548 (0.0719)	0.4128 (0.0578)	0.4351 (0.0601)	0.5415 (0.0699)

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	0.1136
	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	0.7440
	Confidence Interval	() 95%; 0.5158 to 1.0733
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1389
	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	0.1887
	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	0.7842
	Confidence Interval	() 95%; 0.5456 to 1.1271
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1449
	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	0.8925
	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	0.9761
	Confidence Interval	() 95%; 0.6869 to 1.3870
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.1747
	Estimation Comments	Form 12 mcg minus Placebo

60. 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	235	232	234	233
Atrial fibrillation	0.9 0.4%	0.0 0%	0.9 0.4%	0.0 0%
Sinus tachycardia	0.0 0%	0.0 0%	0.0 0%	0.9 0.4%
Acute coronary syndrome	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Acute myocardial infarction	0.0 0%	0.0 0%	0.4 0.2%	0.0 0%
Angina unstable	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Myocardial infarction	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Ventricular extrasystoles	0.4 0.2%	0.4 0.2%	0.0 0%	0.4 0.2%
Alanine aminotransferase increased	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Aspartate aminotransferase increased	0.0 0%	0.0 0%	0.0 0%	0.4 0.2%
Blood creatine phosphokinase increased	0.0 0%	0.0 0%	0.0 0%	0.4 0.2%
Electrocardiogram ST segment depression	0.0 0%	0.4 0.2%	0.0 0%	0.0 0%
Electrocardiogram T wave inversion	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%
Gamma-glutamyltransferase increased	0.4 0.2%	0.0 0%	0.0 0%	0.0 0%

61. 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 study 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	182	216	0
Geometric Mean (Geometric Coefficient of Variation) [pg/mL]	3.920 (50.510)	6.977 (68.643)

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	(2-Sided) 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
	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 (Net)
	Estimated Value	0.525
	Confidence Interval	(2-Sided) 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 (Net)
	Estimated Value	0.355
	Confidence Interval	(2-Sided) 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	48/235 (20.4%)		34/232 (14.7%)		41/234 (17.5%)		36/233 (15.5%)
Cardiac disorders
Acute coronary syndrome	2/235 (0.9%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Acute left ventricular failure	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Acute myocardial infarction	0/235 (0%)		0/232 (0%)		3/234 (1.3%)		0/233 (0%)
Angina pectoris	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Angina unstable	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Arrhythmia	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Atrial fibrillation	2/235 (0.9%)		2/232 (0.9%)		0/234 (0%)		0/233 (0%)
Cardiac arrest	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Cardiac failure	0/235 (0%)		2/232 (0.9%)		0/234 (0%)		0/233 (0%)
Cardiac failure acute	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Cardiac failure congestive	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Cardio-respiratory arrest	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Cardiopulmonary failure	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Cor pulmonale	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Coronary artery disease	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Myocardial infarction	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Myocardial ischaemia	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Right ventricular failure	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Tachycardia	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Ventricular extrasystoles	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Ear and labyrinth disorders
Vertigo	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Eye disorders
Amaurosis fugax	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Gastrointestinal disorders
Abdominal pain	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Diarrhoea	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		1/233 (0.4%)
Gastric polyps	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Gastrointestinal haemorrhage	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Ileus	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Nausea	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Volvulus	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Vomiting	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
General disorders
Asthenia	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Chest pain	0/235 (0%)		1/232 (0.4%)		1/234 (0.4%)		0/233 (0%)
Chills	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Death	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		1/233 (0.4%)
Influenza like illness	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Multi-organ failure	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Oedema peripheral	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Pain	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Pyrexia	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Sudden cardiac death	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Hepatobiliary disorders
Acute hepatic failure	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Cholecystitis acute	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Immune system disorders
Anaphylactic shock	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Infections and infestations
Bronchitis	2/235 (0.9%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Carbuncle	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Cellulitis pharyngeal	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Cholecystitis infective	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Cystitis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Incision site infection	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Infective exacerbation of chronic obstructive airways disease	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Kidney infection	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Lobar pneumonia	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Lower respiratory tract infection	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Nasopharyngitis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Peritonsillar abscess	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Pneumonia	2/235 (0.9%)		3/232 (1.3%)		7/234 (3%)		4/233 (1.7%)
Pulmonary tuberculosis	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Pyelonephritis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Respiratory tract infection	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Sepsis	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Tuberculosis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Upper respiratory tract infection	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Viral infection	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Injury, poisoning and procedural complications
Arthropod sting	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Femur fracture	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Fibula fracture	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Foot fracture	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Joint dislocation	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Laceration	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Patella fracture	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Post procedural complication	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Post procedural haematuria	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Postoperative ileus	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Rib fracture	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Road traffic accident	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Tendon rupture	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Metabolism and nutrition disorders
Dehydration	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Diabetic ketoacidosis	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Malnutrition	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/235 (0%)		0/232 (0%)		2/234 (0.9%)		0/233 (0%)
Intervertebral disc protrusion	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		2/233 (0.9%)
Meniscal degeneration	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoma benign	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Bladder cancer	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Breast cancer	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Hepatic neoplasm malignant	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Laryngeal cancer	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Lung adenocarcinoma	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Lung neoplasm malignant	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		1/233 (0.4%)
Malignant melanoma	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Metastases to lung	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Oesophageal carcinoma	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Prostate cancer	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Prostate cancer recurrent	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Squamous cell carcinoma	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Nervous system disorders
Cerebral ischaemia	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Cerebrovascular accident	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Dizziness	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Hypoxic-ischaemic encephalopathy	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Ischaemic stroke	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Syncope	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Transient ischaemic attack	2/235 (0.9%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Tremor	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Psychiatric disorders
Depression	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Psychotic disorder	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Renal and urinary disorders
Hydronephrosis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Renal failure acute	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Prostatitis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Bronchiectasis	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Chronic obstructive pulmonary disease	18/235 (7.7%)		14/232 (6%)		17/234 (7.3%)		18/233 (7.7%)
Dyspnoea	1/235 (0.4%)		1/232 (0.4%)		1/234 (0.4%)		2/233 (0.9%)
Epistaxis	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Haemoptysis	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Hypoxia	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Mediastinal mass	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Pleural effusion	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Pneumothorax	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		1/233 (0.4%)
Pulmonary embolism	0/235 (0%)		0/232 (0%)		3/234 (1.3%)		1/233 (0.4%)
Respiratory failure	3/235 (1.3%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Skin and subcutaneous tissue disorders
Skin ulcer	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Surgical and medical procedures
Cholecystectomy	0/235 (0%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Mastoidectomy	0/235 (0%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Vascular disorders
Arteriosclerosis obliterans	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Deep vein thrombosis	1/235 (0.4%)		0/232 (0%)		1/234 (0.4%)		0/233 (0%)
Hypertensive crisis	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Hypertensive emergency	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
Hypovolaemic shock	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		1/233 (0.4%)
Venous occlusion	1/235 (0.4%)		0/232 (0%)		0/234 (0%)		0/233 (0%)
Venous thrombosis	0/235 (0%)		1/232 (0.4%)		0/234 (0%)		0/233 (0%)
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	100/235 (42.6%)		103/232 (44.4%)		101/234 (43.2%)		105/233 (45.1%)
General disorders
Pyrexia	7/235 (3%)		6/232 (2.6%)		12/234 (5.1%)		9/233 (3.9%)
Infections and infestations
Bronchitis	7/235 (3%)		13/232 (5.6%)		10/234 (4.3%)		8/233 (3.4%)
Nasopharyngitis	22/235 (9.4%)		36/232 (15.5%)		28/234 (12%)		23/233 (9.9%)
Upper respiratory tract infection	18/235 (7.7%)		14/232 (6%)		15/234 (6.4%)		21/233 (9%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	51/235 (21.7%)		40/232 (17.2%)		48/234 (20.5%)		51/233 (21.9%)
Cough	16/235 (6.8%)		6/232 (2.6%)		12/234 (5.1%)		14/233 (6%)
Dyspnoea	10/235 (4.3%)		10/232 (4.3%)		3/234 (1.3%)		17/233 (7.3%)

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