12 / 48 wk Pivotal PFT vs PBO in COPD II

Randomised, Double-blind, 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 mcg [2 Actuations of 2.5 mcg] and 10 mcg [2 Actuations of 5 mcg]) Delivered by the Respimat® Inhaler, in Patients With Chronic Obstructive Pulmonary Disease (COPD

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00782509

Enrollment

644

Registered

2008-10-31

Start date

2009-02-28

Completion date

Unknown

Last updated

2014-06-27

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pulmonary Disease, Chronic Obstructive

Brief summary

This primary objective of this study is to compare two doses of BI 1744 CL inhalation solution delivered by the Respimat® inhaler once daily to placebo in patients with chronic obstructive pulmonary disease (COPD).

Interventions

DRUGOlodaterol (BI 1744)

Comparison of low and high doses on efficacy and safety in COPD patients

DRUGPlacebo

Olodaterol (BI 1744) placebo inhaled orally once daily from the Respimat inhaler

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE

Eligibility

Sex/Gender

ALL

Age

40 Years to No maximum

Healthy volunteers

Inclusion criteria

* All patients must have a diagnosis of chronic obstructive pulmonary disease * Male or female patients, 40 years of age or older Patients must be current or ex-smokers with a smoking history of more than 10 pack years Post bronchodilator FEV1 \<80% predicted and post-bronchodilator FEV1/FVC \<70%

Exclusion criteria

* Patients with a significant disease other than COPD * Patients with a history of asthma * Patients with any of the following conditions: a history of myocardial infarction within 1 year of screening visit (Visit 1) unstable or life-threatening cardiac arrhythmia. have been hospitalized 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 (patients with treated basal cell carcinoma are allowed) a history of life-threatening pulmonary obstruction a history of cystic fibrosis

Design outcomes

Primary

Measure	Time frame	Description
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (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 Day 85	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.
Trough FEV1 Response at Day 85 (12 Weeks)	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h and - 10 mins prior to study drug at Day 85.	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.

Secondary

Measure	Time frame	Description
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 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 FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 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 -1h, -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 FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 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 FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 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 FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.
Trough FEV1 Response After 2 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks	Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed a -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FEV1 Response After 6 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks	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.
Trough FEV1 Response After 18 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks	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.
Trough FEV1 Response After 24 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks	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.
Trough FEV1 Response After 32 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks	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.
Trough FEV1 Response After 40 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks	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.
Trough FEV1 Response After 48 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks	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.
Peak FEV1 (0-3h) Response At Day 1	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1	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.
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.
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.
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.
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.
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.
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1	Response was defined as change from baseline. Baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 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 FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
FVC Area Under Curve 0-3 Hours (AUC 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 FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
FVC Area Under Curve 0-3 Hours (AUC 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 FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
FVC Area Under Curve 0-3 Hours (AUC 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 FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
FVC Area Under Curve 0-3 Hours (AUC 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 FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect. FVC AUC 0-3h was calculated using the trapezoidal rule, divided by the observation time to report in litres.
Trough FVC Response After 2 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 2 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 6 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 6 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 12 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 12 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 18 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 18 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 24 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 24 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 32 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 32 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 40 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 40 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Trough FVC Response After 48 Weeks	1 h and 10 min prior to dose on the first day of randomized treatment (baseline) and -1 h (if available) and - 10 mins prior to study drug after 48 weeks	Response was defined as change from baseline. Baseline trough FVC was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FVC is defined as the FVCs obtained at -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FVCs if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
FVC Peak (0-3h) Response At Day 1	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1	Response was defined as change from baseline. Baseline FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours aftertreatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
FVC Peak (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 FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
FVC Peak (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 FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Weekly Mean of Daily (24h) Rescue Use	Week 48	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each 24 hour period during week 48.
FVC Peak (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 FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
FVC Peak (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 FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
FVC Peak (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 FVC peak (0-3h) was defined as the mean of the available pre-dose FVC peak (0-3h) values prior to first dose of randomized treatment. FVC Peak (0-3h) values were obtained within 0 - 3 hours after treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.
Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)	Response was defined as change from baseline. Study baseline FVC was defined as the mean of the available pre-dose FVC values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FVC AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	immediately upon arising (before drug administration) from Screening to week 48	Weekly mean pre-dose morning peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.
Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	at bedtime from Screening to week 48	Weekly mean evening peak expiratory flow rate (PEF) at 48 weeks. PEFR measurements recorded by means of an e-Diary on a daily basis. This e-Diary was used to record the twice daily PEFs, study drug use, and rescue salbutamol (albuterol) use. The best of three readings for each measurement was recorded.
Weekly Mean of Daily Daytime Rescue Use	Week 48	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each day during week 48.
Weekly Mean of Daily Nighttime Rescue Use	Week 48	The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each night during week 48.
Patient's Global Rating at Week 6	Week 6 visit	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Patient's Global Rating at Week 12	Week 12 visit	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Patient's Global Rating at Week 24	Week 24 visit	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
Patient's Global Rating at Week 48	Week 48 visit	Patients were asked to rate their respiratory condition relative to their condition prior to the first dose of study medication. The scale is a seven point scale: 1=very much better, 2=much better,3=a little better,4=no change,5=a little worse,6=much worse,7=very much worst.
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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval.
Time to First Chronic Obstructive Pulmonary Disease (COPD) 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. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval.
Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	1 hour (h) and 10 minutes (min) prior to dose on first day of randomized treatment (baseline) and -1h and -10 min, 5 min, 15 min, 30 min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h relative to dose at Day 85 (12 weeks)	Response was defined as change from baseline. Study baseline FEV1 was defined as the mean of the available pre-dose FEV1 values prior to the first dose of randomized treatment. Means are adjusted using a non-mixed effects model with treatment (trt), tio stratum, baseline as fixed effects. FEV1 AUC 0-12h was calculated from 0-12 hours post-dose using the trapezoidal rule, divided by the observation time (12h) to report in litres.
Number of COPD Exacerbations	Baseline to end of study at week 48 visit	Mean number of COPD exacerbations per patient years. Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria.
Number of COPD Exacerbations Requiring Hospitalization	Baseline to end of study at week 48 visit	Mean number of COPD exacerbations requiring hospitalization per patient years. Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization.
Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	Baseline to end of study at 48 weeks.	Mean number of moderate COPD exacerbations per patient years. Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Moderate exacerbations were defined as exacerbations which did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids.
Changes in Safety Parameters Related to Treatment	48 weeks	Occurence of bronchoconstriction, cardiac disorders and investigations related to treatment. Bronchoconstriction is defined as any of the following events: Drop in trough FEV1 \>= 15%, Rescue medication use within 30 min of inhaling randomized treatment on a clinic test day or Cough, wheeze, or dyspnoea AE within 30 min of inhaling randomized treatment on a clinic test day.
Change From Baseline in Potassium	Day 1 and at 12, 24 and 48 weeks	Laboratory testing: Average change from baseline of potassium measured. The laboratory tests at Day 1 were considered the baseline measurements.
Time to First Moderate 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. Moderate exacerbations were defined as exacerbations which did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval..
Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1	1 hour (h) and 10 minutes (min) prior to dose on the first day of randomized treatment (baseline) to -10 min, 5 min, 15 min, 30 min, 1 h, 2 h, and 3 h relative to dose at Day 1	Response was defined as change from baseline. Baseline FEV1 was defined as the mean of the -1 h and -10 min measurements performed just prior to administration of the first dose of randomized treatment. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit interaction as fixed categorical effects, baseline and baseline-by-visit interaction as fixed continuous covariates and patient as random effect. FEV1 AUC 0-3h was calculated from 0-3 hours post-dose using the trapezoidal rule, divided by the observation time (3h) to report in litres.

Countries

China, Germany, Taiwan, United States

Participant flow

Pre-assignment details

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

Participants by arm

Arm	Count
Placebo Matching Placebo delivered by the Respimat Inhaler.	216
Olo 5 mcg qd Olodaterol 5 mcg qd (morning) delivered by the Respimat Inhaler.	209
Olo 10 mcg qd Olodaterol 10 mcg qd (morning) delivered by the Respimat Inhaler.	217
Total	642

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	20	10	20
Overall Study	Lack of Efficacy	10	5	2
Overall Study	Lost to Follow-up	1	2	3
Overall Study	Non compliance with protocol	2	0	0
Overall Study	Other reasons not stated above	5	2	3
Overall Study	Withdrawal by Subject	3	5	8

Baseline characteristics

Characteristic	Olo 10 mcg qd	Placebo	Total	Olo 5 mcg qd
Age, Continuous	65.4 years STANDARD_DEVIATION 9.7	63.8 years STANDARD_DEVIATION 8.3	64.6 years STANDARD_DEVIATION 8.8	64.7 years STANDARD_DEVIATION 8.1
Sex: Female, Male Female	65 Participants	64 Participants	186 Participants	57 Participants
Sex: Female, Male Male	152 Participants	152 Participants	456 Participants	152 Participants
Tiotropium (Tio) Use Stratum Non-tiotropium	173 Number of participants	175 Number of participants	518 Number of participants	170 Number of participants
Tiotropium (Tio) Use Stratum Tiotropium	44 Number of participants	41 Number of participants	124 Number of participants	39 Number of participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	75 / 216	71 / 209	81 / 217
serious Total, serious adverse events	32 / 216	32 / 209	37 / 217

Outcome results

Primary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)

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 Day 85

Population: Full analysis set (FAS). FAS is defined as all randomized patients who received at least one dose of treatment and had both baseline data and at least one post-baseline measurement at or before Day 85 (12 weeks) for either co-primary efficacy variable.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)	0.008 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)	0.159 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)	0.152 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.116, 0.185]Mixed Models Analysis

p-value: <0.000195% CI: [0.11, 0.177]Mixed Models Analysis

Primary

Trough FEV1 Response at Day 85 (12 Weeks)

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 and - 10 mins prior to study drug at Day 85.

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response at Day 85 (12 Weeks)	-0.003 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response at Day 85 (12 Weeks)	0.044 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response at Day 85 (12 Weeks)	0.045 Liter	Standard Error 0.014

p-value: 0.011695% CI: [0.011, 0.084]Mixed Models Analysis

p-value: 0.009595% CI: [0.012, 0.085]Mixed Models Analysis

Secondary

Change From Baseline in Potassium

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

Time frame: Day 1 and at 12, 24 and 48 weeks

Population: Treated set.

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Change From Baseline in Potassium	-0.0 mmol/L	Standard Deviation 0.4
Olo 5 mcg qd	Change From Baseline in Potassium	-0.0 mmol/L	Standard Deviation 0.4
Olo 10 mcg qd	Change From Baseline in Potassium	0.0 mmol/L	Standard Deviation 0.3

Secondary

Changes in Safety Parameters Related to Treatment

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

Time frame: 48 weeks

Population: Treated set.

Arm	Measure	Group	Value (NUMBER)
Placebo	Changes in Safety Parameters Related to Treatment	Bundle branch block left	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Supraventricular extrasystoles	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Electrocardiogram QT prolonged	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Atrioventricular block second degree	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Atrial fibrillation	0.5 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Blood glucose increased	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Atrioventricular block first degree	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Atrioventricular block	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Palpitations	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Ventricular tachycardia	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Sinus tachycardia	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Bronchoconstriction	13.9 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Ventricular extrasystoles	0.0 percentage of participants
Placebo	Changes in Safety Parameters Related to Treatment	Sinus bradycardia	0.0 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Bundle branch block left	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Bronchoconstriction	3.3 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Blood glucose increased	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Electrocardiogram QT prolonged	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Ventricular tachycardia	1.9 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Ventricular extrasystoles	1.0 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Supraventricular extrasystoles	1.0 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Atrial fibrillation	0.0 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block first degree	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block second degree	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Palpitations	0.0 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Sinus bradycardia	0.5 percentage of participants
Olo 5 mcg qd	Changes in Safety Parameters Related to Treatment	Sinus tachycardia	0.5 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Sinus bradycardia	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block second degree	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Ventricular extrasystoles	1.8 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Ventricular tachycardia	0.5 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Bundle branch block left	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Electrocardiogram QT prolonged	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Bronchoconstriction	5.5 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Palpitations	0.5 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Blood glucose increased	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Atrial fibrillation	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Sinus tachycardia	0.0 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Atrioventricular block first degree	0.5 percentage of participants
Olo 10 mcg qd	Changes in Safety Parameters Related to Treatment	Supraventricular extrasystoles	1.4 percentage of participants

Secondary

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

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

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

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.010 Liter	Standard Error 0.021
Olo 5 mcg qd	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.120 Liter	Standard Error 0.02
Olo 10 mcg qd	Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.100 Liter	Standard Error 0.02

p-value: <0.000195% CI: [0.057, 0.162]ANCOVA

p-value: 0.001195% CI: [0.036, 0.143]Mixed Models Analysis

Secondary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks

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

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks	-0.010 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks	0.155 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks	0.126 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.131, 0.2]Mixed Models Analysis

p-value: <0.000195% CI: [0.102, 0.171]Mixed Models Analysis

Secondary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks	0.025 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks	0.188 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks	0.177 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.13, 0.197]Mixed Models Analysis

p-value: <0.000195% CI: [0.119, 0.186]Mixed Models Analysis

Secondary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks	-0.030 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks	0.132 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks	0.128 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.127, 0.196]Mixed Models Analysis

p-value: <0.000195% CI: [0.123, 0.193]Mixed Models Analysis

Secondary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks	0.010 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks	0.180 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks	0.171 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.135, 0.203]Mixed Models Analysis

p-value: <0.000195% CI: [0.127, 0.195]Mixed Models Analysis

Secondary

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1

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 at Day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1	0.025 Liter	Standard Error 0.013
Olo 5 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1	0.189 Liter	Standard Error 0.013
Olo 10 mcg qd	Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1	0.196 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.131, 0.197]Mixed Models Analysis

p-value: <0.000195% CI: [0.138, 0.204]Mixed Models Analysis

Secondary

Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

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

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.057 Liter	Standard Error 0.036
Olo 5 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.199 Liter	Standard Error 0.035
Olo 10 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)	0.212 Liter	Standard Error 0.036

p-value: 0.002895% CI: [0.049, 0.235]ANCOVA

p-value: 0.001395% CI: [0.061, 0.25]ANCOVA

Secondary

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks

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

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks	0.096 Liter	Standard Error 0.026
Olo 5 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks	0.338 Liter	Standard Error 0.026
Olo 10 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks	0.323 Liter	Standard Error 0.026

p-value: <0.000195% CI: [0.174, 0.31]Mixed Models Analysis

p-value: <0.000195% CI: [0.159, 0.294]Mixed Models Analysis

Secondary

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1

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 at Day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1	0.052 Liter	Standard Error 0.026
Olo 5 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1	0.383 Liter	Standard Error 0.026
Olo 10 mcg qd	Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1	0.384 Liter	Standard Error 0.026

p-value: <0.000195% CI: [0.263, 0.399]Mixed Models Analysis

p-value: <0.000195% CI: [0.265, 0.4]Mixed Models Analysis

Secondary

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks	0.046 Liter	Standard Error 0.026
Olo 5 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks	0.284 Liter	Standard Error 0.027
Olo 10 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks	0.291 Liter	Standard Error 0.026

p-value: <0.000195% CI: [0.17, 0.308]Mixed Models Analysis

p-value: <0.000195% CI: [0.176, 0.314]Mixed Models Analysis

Secondary

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks	0.062 Liter	Standard Error 0.027
Olo 5 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks	0.303 Liter	Standard Error 0.027
Olo 10 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks	0.281 Liter	Standard Error 0.026

p-value: <0.000195% CI: [0.171, 0.311]Mixed Models Analysis

p-value: <0.000195% CI: [0.15, 0.289]Mixed Models Analysis

Secondary

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks	0.053 Liter	Standard Error 0.027
Olo 5 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks	0.271 Liter	Standard Error 0.027
Olo 10 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks	0.271 Liter	Standard Error 0.027

p-value: <0.000195% CI: [0.147, 0.288]Mixed Models Analysis

p-value: <0.000195% CI: [0.148, 0.288]Mixed Models Analysis

Secondary

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks	0.048 Liter	Standard Error 0.026
Olo 5 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks	0.312 Liter	Standard Error 0.027
Olo 10 mcg qd	FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks	0.294 Liter	Standard Error 0.026

p-value: <0.000195% CI: [0.195, 0.332]Mixed Models Analysis

p-value: <0.000195% CI: [0.178, 0.315]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response After 12 Weeks

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

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response After 12 Weeks	0.213 Liter	Standard Error 0.028
Olo 5 mcg qd	FVC Peak (0-3h) Response After 12 Weeks	0.439 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response After 12 Weeks	0.422 Liter	Standard Error 0.027

p-value: <0.000195% CI: [0.154, 0.298]Mixed Models Analysis

p-value: <0.000195% CI: [0.137, 0.281]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response After 24 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response After 24 Weeks	0.223 Liter	Standard Error 0.028
Olo 5 mcg qd	FVC Peak (0-3h) Response After 24 Weeks	0.449 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response After 24 Weeks	0.429 Liter	Standard Error 0.028

p-value: <0.000195% CI: [0.153, 0.299]Mixed Models Analysis

p-value: <0.000195% CI: [0.133, 0.279]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response After 2 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response After 2 Weeks	0.254 Liter	Standard Error 0.027
Olo 5 mcg qd	FVC Peak (0-3h) Response After 2 Weeks	0.479 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response After 2 Weeks	0.464 Liter	Standard Error 0.027

p-value: <0.000195% CI: [0.153, 0.296]Mixed Models Analysis

p-value: <0.000195% CI: [0.139, 0.281]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response After 48 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response After 48 Weeks	0.208 Liter	Standard Error 0.028
Olo 5 mcg qd	FVC Peak (0-3h) Response After 48 Weeks	0.415 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response After 48 Weeks	0.419 Liter	Standard Error 0.028

p-value: <0.000195% CI: [0.133, 0.28]Mixed Models Analysis

p-value: <0.000195% CI: [0.138, 0.285]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response After 6 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response After 6 Weeks	0.183 Liter	Standard Error 0.028
Olo 5 mcg qd	FVC Peak (0-3h) Response After 6 Weeks	0.451 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response After 6 Weeks	0.434 Liter	Standard Error 0.027

p-value: <0.000195% CI: [0.196, 0.34]Mixed Models Analysis

p-value: <0.000195% CI: [0.179, 0.323]Mixed Models Analysis

Secondary

FVC Peak (0-3h) Response At Day 1

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

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 at Day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	FVC Peak (0-3h) Response At Day 1	0.202 Liter	Standard Error 0.027
Olo 5 mcg qd	FVC Peak (0-3h) Response At Day 1	0.534 Liter	Standard Error 0.028
Olo 10 mcg qd	FVC Peak (0-3h) Response At Day 1	0.535 Liter	Standard Error 0.027

p-value: <0.000195% CI: [0.261, 0.403]Mixed Models Analysis

p-value: <0.000195% CI: [0.263, 0.403]Mixed Models Analysis

Secondary

Number of COPD Exacerbations

Mean number of COPD exacerbations per patient years. Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria.

Time frame: Baseline to end of study at week 48 visit

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Number of COPD Exacerbations	0.4590 COPD exacerbations	Standard Error 0.0687
Olo 5 mcg qd	Number of COPD Exacerbations	0.5453 COPD exacerbations	Standard Error 0.0765
Olo 10 mcg qd	Number of COPD Exacerbations	0.5885 COPD exacerbations	Standard Error 0.0799

p-value: 0.363795% CI: [0.8188, 1.7234]Negative binomial regression

p-value: 0.185395% CI: [0.8874, 1.8527]Negative binomial regression

Secondary

Number of COPD Exacerbations Requiring Hospitalization

Mean number of COPD exacerbations requiring hospitalization per patient years. Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization.

Time frame: Baseline to end of study at week 48 visit

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Number of COPD Exacerbations Requiring Hospitalization	0.0786 COPD exacerbations	Standard Error 0.0273
Olo 5 mcg qd	Number of COPD Exacerbations Requiring Hospitalization	0.0811 COPD exacerbations	Standard Error 0.0268
Olo 10 mcg qd	Number of COPD Exacerbations Requiring Hospitalization	0.0886 COPD exacerbations	Standard Error 0.0287

p-value: 0.945595% CI: [0.4244, 2.5063]Negative binomial regression

p-value: 0.788395% CI: [0.4696, 2.7064]Negative binomial regression

Secondary

Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

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

Time frame: Baseline to end of study at 48 weeks.

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

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	0.3375 COPD exacerbations	Standard Error 0.0587
Olo 5 mcg qd	Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	0.4335 COPD exacerbations	Standard Error 0.0699
Olo 10 mcg qd	Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations	0.4513 COPD exacerbations	Standard Error 0.0701

p-value: 0.251495% CI: [0.837, 1.9717]Negative binomial regression

p-value: 0.180795% CI: [0.8735, 2.0474]Negative binomial regression

Secondary

Patient's Global Rating at Week 12

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

Time frame: Week 12 visit

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Patient's Global Rating at Week 12	3.2 Point on scale	Standard Error 0.1
Olo 5 mcg qd	Patient's Global Rating at Week 12	2.9 Point on scale	Standard Error 0.1
Olo 10 mcg qd	Patient's Global Rating at Week 12	3.0 Point on scale	Standard Error 0.1

p-value: 0.002895% CI: [-0.5, -0.1]Mixed Models Analysis

p-value: 0.016995% CI: [-0.5, 0]Mixed Models Analysis

Secondary

Patient's Global Rating at Week 24

Time frame: Week 24 visit

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Patient's Global Rating at Week 24	3.3 Point on scale	Standard Error 0.1
Olo 5 mcg qd	Patient's Global Rating at Week 24	3.0 Point on scale	Standard Error 0.1
Olo 10 mcg qd	Patient's Global Rating at Week 24	2.9 Point on scale	Standard Error 0.1

p-value: 0.01895% CI: [-0.5, 0]Mixed Models Analysis

p-value: 0.001595% CI: [-0.6, -0.1]Mixed Models Analysis

Secondary

Patient's Global Rating at Week 48

Time frame: Week 48 visit

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Patient's Global Rating at Week 48	3.3 Point on scale	Standard Error 0.1
Olo 5 mcg qd	Patient's Global Rating at Week 48	3.1 Point on scale	Standard Error 0.1
Olo 10 mcg qd	Patient's Global Rating at Week 48	3.0 Point on scale	Standard Error 0.1

p-value: 0.131395% CI: [-0.4, 0]Mixed Models Analysis

p-value: 0.008995% CI: [-0.5, -0.1]Mixed Models Analysis

Secondary

Patient's Global Rating at Week 6

Time frame: Week 6 visit

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Patient's Global Rating at Week 6	3.3 Point on scale	Standard Error 0.1
Olo 5 mcg qd	Patient's Global Rating at Week 6	3.0 Point on scale	Standard Error 0.1
Olo 10 mcg qd	Patient's Global Rating at Week 6	2.9 Point on scale	Standard Error 0.1

p-value: 0.012295% CI: [-0.5, -0.1]Mixed Models Analysis

p-value: 0.000895% CI: [-0.6, -0.1]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response 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.

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response After 12 Weeks	0.088 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response After 12 Weeks	0.232 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response After 12 Weeks	0.217 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.108, 0.18]Mixed Models Analysis

p-value: <0.000195% CI: [0.094, 0.166]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response After 24 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response After 24 Weeks	0.062 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response After 24 Weeks	0.226 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response After 24 Weeks	0.197 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.128, 0.201]Mixed Models Analysis

p-value: <0.000195% CI: [0.098, 0.171]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response After 2 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response After 2 Weeks	0.104 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response After 2 Weeks	0.259 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response After 2 Weeks	0.251 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.119, 0.19]Mixed Models Analysis

p-value: <0.000195% CI: [0.111, 0.182]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response After 48 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response After 48 Weeks	0.041 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response After 48 Weeks	0.197 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response After 48 Weeks	0.198 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.118, 0.192]Mixed Models Analysis

p-value: <0.000195% CI: [0.12, 0.194]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response After 6 Weeks

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response After 6 Weeks	0.080 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response After 6 Weeks	0.252 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response After 6 Weeks	0.246 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.136, 0.209]Mixed Models Analysis

p-value: <0.000195% CI: [0.13, 0.202]Mixed Models Analysis

Secondary

Peak FEV1 (0-3h) Response At Day 1

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 at Day 1

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Peak FEV1 (0-3h) Response At Day 1	0.099 Liter	Standard Error 0.014
Olo 5 mcg qd	Peak FEV1 (0-3h) Response At Day 1	0.267 Liter	Standard Error 0.014
Olo 10 mcg qd	Peak FEV1 (0-3h) Response At Day 1	0.276 Liter	Standard Error 0.013

p-value: <0.000195% CI: [0.132, 0.203]Mixed Models Analysis

p-value: <0.000195% CI: [0.142, 0.212]Mixed Models Analysis

Secondary

Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval.

Time frame: Baseline to end of study at 48 weeks.

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

Arm	Measure	Value (MEAN)
Placebo	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	306.0 days
Olo 5 mcg qd	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	259.0 days
Olo 10 mcg qd	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	225.0 days
Olo 5 mcg qd (Non-tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	315.0 days
Olo 10 mcg qd (Tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	219.0 days
Olo 10 mcg qd(Non-tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	216.0 days

p-value: 0.985395% CI: [0.687, 1.436]Log Rank

p-value: 0.234495% CI: [0.873, 1.763]Log Rank

Secondary

Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization

Qualifying events of COPD were specifically pre-defined in the protocol. Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. These exacerbations required hospitalization. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor. Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval.

Time frame: Baseline to end of study at 48 weeks.

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

Arm	Measure	Value (MEAN)
Placebo	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days
Olo 5 mcg qd	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days
Olo 10 mcg qd	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days
Olo 5 mcg qd (Non-tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days
Olo 10 mcg qd (Tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days
Olo 10 mcg qd(Non-tiotropium)	Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization	NA days

p-value: 0.903595% CI: [0.463, 2.38]Log Rank

p-value: 0.930495% CI: [0.415, 2.209]Log Rank

Secondary

Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Qualifying events of COPD were specifically pre-defined in the protocol.Other respiratory related events were evaluated by the investigator to see if they met the pre-defined criteria. Moderate exacerbations were defined as exacerbations which did not lead to hospitalization but included treatment with antibiotics and/or systemic steroids. Time to event was measured from the beginning of treatment. Cox regression analysis of treatment effect using tiotropium stratum as a stratification factor.Due to the limited number of events some statistics were not able to be calculated and are listed as N/A or are blank. The measured values presented are actually the First Quartile and 95% confidence interval..

Time frame: Baseline to end of study at 48 weeks.

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

Arm	Measure	Value (MEAN)
Placebo	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	NA days
Olo 5 mcg qd	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	362.0 days
Olo 10 mcg qd	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	NA days
Olo 5 mcg qd (Non-tiotropium)	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	NA days
Olo 10 mcg qd (Tiotropium)	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	225.0 days
Olo 10 mcg qd(Non-tiotropium)	Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation	308.0 days

p-value: 0.66995% CI: [0.717, 1.657]Log Rank

p-value: 0.143795% CI: [0.902, 2.002]Log Rank

Secondary

Trough FEV1 Response After 18 Weeks

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 after 18 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 18 Weeks	-0.007 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 18 Weeks	0.062 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 18 Weeks	0.037 Liter	Standard Error 0.014

p-value: 0.000295% CI: [0.032, 0.106]Mixed Models Analysis

p-value: 0.018695% CI: [0.007, 0.081]Mixed Models Analysis

Secondary

Trough FEV1 Response After 24 Weeks

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 after 24 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 24 Weeks	-0.036 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 24 Weeks	0.033 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 24 Weeks	0.022 Liter	Standard Error 0.014

p-value: 0.000395% CI: [0.032, 0.106]Mixed Models Analysis

p-value: 0.00295% CI: [0.021, 0.095]Mixed Models Analysis

Secondary

Trough FEV1 Response After 2 Weeks

Response was defined as change from baseline. Baseline trough FEV1 was defined as the mean of the -1 hour and -10 minute measurements performed just prior to first dose of randomized treatment. Trough FEV1 is defined as the FEV1 performed a -10 mins prior to study drug inhalation as the end of the dosing interval or the mean of -1h and -10 min FEV1s if both available. Means are adjusted using a mixed effects model with treatment (trt), tio stratum, visit, trt-by-visit as fixed categorical effects, baseline and baseline-by-visit as fixed continuous covariates and patient as random effect.

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 after 2 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 2 Weeks	0.013 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 2 Weeks	0.066 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 2 Weeks	0.078 Liter	Standard Error 0.014

p-value: 0.004395% CI: [0.017, 0.089]Mixed Models Analysis

p-value: 0.000595% CI: [0.028, 0.101]Mixed Models Analysis

Secondary

Trough FEV1 Response After 32 Weeks

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 after 32 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 32 Weeks	-0.029 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 32 Weeks	0.029 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 32 Weeks	-0.002 Liter	Standard Error 0.014

p-value: 0.002495% CI: [0.02, 0.095]Mixed Models Analysis

p-value: 0.161495% CI: [-0.011, 0.064]Mixed Models Analysis

Secondary

Trough FEV1 Response After 40 Weeks

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 after 40 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 40 Weeks	-0.029 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 40 Weeks	0.033 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 40 Weeks	0.043 Liter	Standard Error 0.014

p-value: 0.001295% CI: [0.025, 0.099]Mixed Models Analysis

p-value: 0.000295% CI: [0.034, 0.109]Mixed Models Analysis

Secondary

Trough FEV1 Response After 48 Weeks

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 after 48 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 48 Weeks	-0.057 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 48 Weeks	0.011 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 48 Weeks	0.014 Liter	Standard Error 0.014

p-value: 0.000495% CI: [0.031, 0.106]Mixed Models Analysis

p-value: 0.000295% CI: [0.033, 0.108]Mixed Models Analysis

Secondary

Trough FEV1 Response After 6 Weeks

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 after 6 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FEV1 Response After 6 Weeks	-0.002 Liter	Standard Error 0.014
Olo 5 mcg qd	Trough FEV1 Response After 6 Weeks	0.071 Liter	Standard Error 0.014
Olo 10 mcg qd	Trough FEV1 Response After 6 Weeks	0.082 Liter	Standard Error 0.014

p-value: <0.000195% CI: [0.037, 0.11]Mixed Models Analysis

p-value: <0.000195% CI: [0.049, 0.121]Mixed Models Analysis

Secondary

Trough FVC Response After 12 Weeks

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

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 after 12 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 12 Weeks	0.043 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 12 Weeks	0.075 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 12 Weeks	0.091 Liter	Standard Error 0.027

p-value: 0.382195% CI: [-0.04, 0.105]Mixed Models Analysis

p-value: 0.191795% CI: [-0.024, 0.12]Mixed Models Analysis

Secondary

Trough FVC Response After 18 Weeks

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 after 18 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 18 Weeks	0.064 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 18 Weeks	0.114 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 18 Weeks	0.098 Liter	Standard Error 0.028

p-value: 0.180895% CI: [-0.023, 0.123]Mixed Models Analysis

p-value: 0.3795% CI: [-0.039, 0.106]Mixed Models Analysis

Secondary

Trough FVC Response After 24 Weeks

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 after 24 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 24 Weeks	0.021 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 24 Weeks	0.066 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 24 Weeks	0.091 Liter	Standard Error 0.028

p-value: 0.231295% CI: [-0.029, 0.118]Mixed Models Analysis

p-value: 0.059695% CI: [-0.003, 0.144]Mixed Models Analysis

Secondary

Trough FVC Response After 2 Weeks

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 after 2 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 2 Weeks	0.054 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 2 Weeks	0.113 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 2 Weeks	0.141 Liter	Standard Error 0.027

p-value: 0.10495% CI: [-0.012, 0.131]Mixed Models Analysis

p-value: 0.017295% CI: [0.015, 0.158]Mixed Models Analysis

Secondary

Trough FVC Response After 32 Weeks

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 after 32 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 32 Weeks	0.061 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 32 Weeks	0.099 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 32 Weeks	0.058 Liter	Standard Error 0.028

p-value: 0.31195% CI: [-0.036, 0.111]Mixed Models Analysis

p-value: 0.942695% CI: [-0.076, 0.071]Mixed Models Analysis

Secondary

Trough FVC Response After 40 Weeks

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 after 40 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 40 Weeks	0.062 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 40 Weeks	0.104 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 40 Weeks	0.131 Liter	Standard Error 0.028

p-value: 0.26895% CI: [-0.032, 0.115]Mixed Models Analysis

p-value: 0.066295% CI: [-0.005, 0.143]Mixed Models Analysis

Secondary

Trough FVC Response After 48 Weeks

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 after 48 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 48 Weeks	-0.008 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 48 Weeks	0.038 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 48 Weeks	0.054 Liter	Standard Error 0.028

p-value: 0.224995% CI: [-0.028, 0.12]Mixed Models Analysis

p-value: 0.099495% CI: [-0.012, 0.136]Mixed Models Analysis

Secondary

Trough FVC Response After 6 Weeks

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 after 6 weeks

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Trough FVC Response After 6 Weeks	0.029 Liter	Standard Error 0.028
Olo 5 mcg qd	Trough FVC Response After 6 Weeks	0.122 Liter	Standard Error 0.028
Olo 10 mcg qd	Trough FVC Response After 6 Weeks	0.147 Liter	Standard Error 0.027

p-value: 0.010695% CI: [0.022, 0.166]Mixed Models Analysis

p-value: 0.001395% CI: [0.046, 0.19]Mixed Models Analysis

Secondary

Weekly Mean Evening Peak Expiratory Flow Rate (PEF)

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

Time frame: at bedtime from Screening to week 48

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	195.502 L/min	Standard Error 3.987
Olo 5 mcg qd	Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	207.958 L/min	Standard Error 4.065
Olo 10 mcg qd	Weekly Mean Evening Peak Expiratory Flow Rate (PEF)	216.155 L/min	Standard Error 3.948

p-value: 0.016995% CI: [2.242, 22.67]ANCOVA

p-value: <0.000195% CI: [10.574, 30.731]ANCOVA

Secondary

Weekly Mean of Daily (24h) Rescue Use

The patient was to record in the e-Diary the number of puffs of salbutamol (albuterol) Metered-Dose Inhaler used each day and night. The weekly mean was calculated by taking the average of the number of puffs of rescue medication used each 24 hour period during week 48.

Time frame: Week 48

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Weekly Mean of Daily (24h) Rescue Use	3.436 Number of puffs	Standard Error 0.193
Olo 5 mcg qd	Weekly Mean of Daily (24h) Rescue Use	2.599 Number of puffs	Standard Error 0.197
Olo 10 mcg qd	Weekly Mean of Daily (24h) Rescue Use	2.158 Number of puffs	Standard Error 0.192

p-value: 0.00195% CI: [-1.333, -0.342]ANCOVA

p-value: <0.000195% CI: [-1.767, -0.789]ANCOVA

Secondary

Weekly Mean of Daily Daytime Rescue Use

Time frame: Week 48

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Weekly Mean of Daily Daytime Rescue Use	1.363 Number of puffs	Standard Error 0.097
Olo 5 mcg qd	Weekly Mean of Daily Daytime Rescue Use	0.947 Number of puffs	Standard Error 0.099
Olo 10 mcg qd	Weekly Mean of Daily Daytime Rescue Use	0.850 Number of puffs	Standard Error 0.097

p-value: 0.001195% CI: [-0.665, -0.167]ANCOVA

p-value: <0.000195% CI: [-0.76, -0.267]ANCOVA

Secondary

Weekly Mean of Daily Nighttime Rescue Use

Time frame: Week 48

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Weekly Mean of Daily Nighttime Rescue Use	2.072 Number of puffs	Standard Error 0.121
Olo 5 mcg qd	Weekly Mean of Daily Nighttime Rescue Use	1.652 Number of puffs	Standard Error 0.123
Olo 10 mcg qd	Weekly Mean of Daily Nighttime Rescue Use	1.312 Number of puffs	Standard Error 0.12

p-value: 0.007795% CI: [-0.729, -0.111]ANCOVA

p-value: <0.000195% CI: [-1.065, -0.456]ANCOVA

Secondary

Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)

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

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

Population: FAS

Arm	Measure	Value (MEAN)	Dispersion
Placebo	Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	182.939 L/min	Standard Error 3.8
Olo 5 mcg qd	Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	196.300 L/min	Standard Error 3.868
Olo 10 mcg qd	Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)	203.873 L/min	Standard Error 3.757

p-value: 0.007295% CI: [3.622, 23.099]ANCOVA

p-value: <0.000195% CI: [11.323, 30.545]ANCOVA

Source: ClinicalTrials.gov · Data processed: Mar 19, 2026

12 / 48 wk Pivotal PFT vs PBO in COPD II

Conditions

Brief summary

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response at Day 85 (12 Weeks)

Trough FEV1 Response at Day 85 (12 Weeks)

Change From Baseline in Potassium

Changes in Safety Parameters Related to Treatment

Forced Expiratory Volume in 1 Second (FEV1) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 24 Weeks

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 2 Weeks

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 48 Weeks

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response After 6 Weeks

Forced Expiratory Volume in One Second (FEV1) Area Under Curve 0-3 Hour (h) (AUC 0-3h) Response At Day 1

Forced Vital Capacity (FVC) Area Under Curve 0-12 h (AUC 0-12h) Response at Day 85 (12 Weeks)

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response After 2 Weeks

Forced Vital Capacity (FVC) Area Under Curve 0-3 Hours (AUC 0-3h) Response At Day 1

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 12 Weeks

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 24 Weeks

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 48 Weeks

FVC Area Under Curve 0-3 Hours (AUC 0-3h) Response After 6 Weeks

FVC Peak (0-3h) Response After 12 Weeks

FVC Peak (0-3h) Response After 24 Weeks

FVC Peak (0-3h) Response After 2 Weeks

FVC Peak (0-3h) Response After 48 Weeks

FVC Peak (0-3h) Response After 6 Weeks

FVC Peak (0-3h) Response At Day 1

Number of COPD Exacerbations

Number of COPD Exacerbations Requiring Hospitalization

Number of Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbations

Patient's Global Rating at Week 12

Patient's Global Rating at Week 24

Patient's Global Rating at Week 48

Patient's Global Rating at Week 6

Peak FEV1 (0-3h) Response After 12 Weeks

Peak FEV1 (0-3h) Response After 24 Weeks

Peak FEV1 (0-3h) Response After 2 Weeks

Peak FEV1 (0-3h) Response After 48 Weeks

Peak FEV1 (0-3h) Response After 6 Weeks

Peak FEV1 (0-3h) Response At Day 1

Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Time to First Chronic Obstructive Pulmonary Disease (COPD) Exacerbation Leading to Hospitalization

Time to First Moderate Chronic Obstructive Pulmonary Disease (COPD) Exacerbation

Trough FEV1 Response After 18 Weeks

Trough FEV1 Response After 24 Weeks

Trough FEV1 Response After 2 Weeks

Trough FEV1 Response After 32 Weeks

Trough FEV1 Response After 40 Weeks

Trough FEV1 Response After 48 Weeks

Trough FEV1 Response After 6 Weeks

Trough FVC Response After 12 Weeks

Trough FVC Response After 18 Weeks

Trough FVC Response After 24 Weeks

Trough FVC Response After 2 Weeks

Trough FVC Response After 32 Weeks

Trough FVC Response After 40 Weeks

Trough FVC Response After 48 Weeks

Trough FVC Response After 6 Weeks

Weekly Mean Evening Peak Expiratory Flow Rate (PEF)

Weekly Mean of Daily (24h) Rescue Use

Weekly Mean of Daily Daytime Rescue Use

Weekly Mean of Daily Nighttime Rescue Use

Weekly Mean Pre-dose Morning Peak Expiratory Flow Rate (PEF)