Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) The FAS included all randomized patients who received at least one dose of study medication. Patients in this group were analyzed according to the treatment to which they were randomized. Missing trough FEV1 values at week 12 were imputed using LOCF with pre-dose trough FEV1.

Transition Dyspnea Index (TDI) captures changes from baseline. The TDI score is based on three domains with each domain scored from -3 (major deterioration) to +3 (major improvement), to give an overall score of -9 to +9, a negative score indicating a deterioration from baseline. A TDI focal score of 1 is considered to be a clinically significant improvement from baseline. Mixed model used baseline TDI, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Patients per treatment group with no missing data were included in this analysis.

SGRQ is a health related quality of life questionnaire consisting of 51 items in three components: symptoms, activity, and impacts. The lowest possible value is zero and the highest 100. Higher values correspond to greater impairment in quality of life. Mixed model used baseline SGRQ, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Individual component score was imputed with LOCF (last observation carried forward).

The time to the first moderate or severe COPD exacerbation was the study day on which the patient experienced first moderate or severe COPD exacerbation. COPD exacerbations are considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations are considered to be severe if treatment for moderate severity and hospitalization were required.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication.

The median values were not estimable.

Participants recorded the number of puffs of rescue medication taken in the previous 12 hours in the morning and evening. The total number of puffs of rescue medication per day over the full 26 weeks was calculated and divided by the total number of days with non-missing rescue medication data to derive the mean daily number of puffs of rescue medication taken for the patient.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. Patients with observations both at baseline and week 26 were included in this analysis

Spirometry was conducted according to internationally accepted standards. FEV1 was measured at all time points up to 4 hours post-dose, and at 23 hours 15 min and 23 hours 45 min, by visit. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. "n" indicates number of patients with observation at each time-point

Spirometry was conducted according to internationally accepted standards. FVC was calculated at each time point up to 4 hours post-dose and at 23 hours 15 min and 23 hours 45 min, by visit. Mixed model used baseline FVC, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. "n" indicates number of patients with observation at each time-point.

The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 12 h post dose at Week 1 Day 1, Week 12 and Week 26 for every patient in the serial spirometry subgroup. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Serial spirometry group, a sub-set of the full analysis set of patients. Twelve hour serial spirometry was conducted in this subset of patients in selected centers at Day 1. At week 12/13 and week 26/27 a 24 hour serial spirometry was performed. "n" is the number of patients with non-missing observations at each time point.

The standardized (with respect to the length of time) area under the curve (AUC) for FEV1 was calculated using trapezoidal rule between 5 min and 23 h 45 min post dose at week12/week 13and week 26/week 27 where available for every patient in the serial spirometry subgroup. Mixed model used baseline FEV1,baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Serial spirometry group, a sub-set of the full analysis set of patients. Twelve hour serial spirometry was conducted in this subset of patients in selected centers at Day 1. At week 12/13 and week 26/27 a 24 hour serial spirometry was performed.

Spirometry was conducted according to internationally accepted standards. Trough FEV1 was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FEV1 readings. Mixed model used baseline FEV1, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.

Trough FVC was defined as the average of the 23 hour 15 minute and 23 hour 45 minute post-dose FVC readings. Mixed model used baseline FVC, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. If one of the 23 h 15 min or 23 h 45 min values are missing then the remaining non-missing value is taken as trough FEV1 or trough FVC. If both values are missing, then their trough FEV1 or trough FVC is regarded as missing

The mean heart rate was collected with a 24 hour Holter monitor in a sub-set of the safety population. The change between baseline and day 1, week 12 and week 26 was calculated. The analysis of the Holter recordings was performed by a central facility. Data on heart rate, heart rate variability, supraventricular and ventricular ectopy were collected and assessed.

The safety set included all patients who received at least one dose of study medication whether or not being randomized. A sub-set of the safety population had 24 hour Holter monitoring. "n" indicates patients with observations both at baseline and each endpoint.

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

The safety set included all patients who received at least one dose of study medication whether or not being randomized. Patients were randomized according to the treatment they received.

One overall rate is calculated for the entire study population. Rate is the number of moderate or severe exacerbations per year = total number of moderate or severe exacerbations for all participants/total number of treatment years for all participants. COPD exacerbations were considered to be moderate if treatment with systemic corticosteroids and/or antibiotics was required. COPD exacerbations were considered to be severe if treatment for moderate severity and hospitalization were required.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication.

The percentage of nights with no nighttime awakenings is defined as the total number of nights with no nighttime awakenings over the 26 week treatment period divided by the total number of night where diary recordings have been made.

Mixed model used baseline nighttime awakenings, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline.

The percentage of days with no daytime symptoms is defined as the total number of days with no daytime symptoms over the 26 week treatment period divided by the total number of days where diary recordings have been made.

Mixed model used baseline daytime symptoms, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline.

The percentage of days able to perform usual daily activities is defined as the total number of days able to perform usual activities over the 26 week treatment period divided by the total number of days where diary recordings have been made.

Mixed model used baseline ability to perform usual daily activities, baseline ICS use, FEV1 prior to inhalation of SABA, and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication. At 26 weeks, the analysis is based on only patients with a value at both baseline and post-baseline.

The daily symptom score was calculated as the sum of the worst of the morning and evening assessments for each symptom (symptoms, cough, wheeze, sputum color/production, and breathlessness). The score can range from 0 to 18 with 0 indicating no symptoms. The higher the score, the worse the symptomatic status. A negative change (lower number) indicates improvement.

Mixed model used baseline symptom variables, baseline inhaled corticosteroid (ICS) use, FEV1 prior to inhalation of short acting beta-agonist (SABA), and FEV1 45 minutes post-inhalation of SABA as covariates.

Full Analysis Set (FAS) included all randomized patients who received at least one dose of study medication.