The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters on Week 12. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment.

Change from baseline in the FEV1 mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in FEV1 + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The overall number of participants analyzed includes all randomized participants with a value at both baseline and week 12. Results for the QBW251 450 mg arm need to be interpreted with caution as the arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

The primary efficacy analysis assessed the effect of QBW251 on the absolute change from baseline in trough FEV1 in liters compared to placebo on Weeks 4, 8, 16, 20 and 24. Forced Expiratory Volume in one second (FEV1) is calculated as the volume of air forcibly exhaled in one second as measured by a spirometer. Baseline measurement was defined as the baseline visit pre-bronchodilator spirometry assessment. A positive trend for change from baseline in FEV1 across the dose range is considered a favorable outcome.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. Results for the QBW251 450 mg arm need to be interpreted with caution as the arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

The E-RS assesses overall daily respiratory COPD symptoms (Total score) and it is derived as the sum of 11 severity items; a higher scores indicate more severe symptoms. E-RS total score has a range of 0 to 40.

Change from baseline in the E-RS Total weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The mean baseline E-RS Total score was the average of the corresponding daily scores from the run-in period.

A negative change from baseline corresponds to improvement in symptoms severity.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. QBW251 450 mg arm was excluded from the analysis as it was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

The E-RS assesses both overall daily respiratory COPD symptoms (Total score) and specific respiratory symptoms using 3 subscales (Breathlessness, Cough & Sputum, and Chest Symptoms). The E-RS comprises 11 severity items and higher scores indicate more severe symptoms. The Cough and Sputum subscale score has a range of 0 to 11 and was derived as the sum of items 2 - 4.

Change from baseline in the E-RS Cough and Sputum weekly mean scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The mean baseline E-RS Cough & Sputum subscale score was the average of the corresponding daily scores from the run-in period. Lower scores in the change from baseline correspond to lower symptom severity.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. QBW251 450 mg arm was excluded from the analysis as it was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

The PGI-S questionnaire is a patient-reported outcomes score that rates the severity of the respiratory symptoms and of cough and mucus. The change in severity scores (Better, No change and Worse) from baseline were reported at weeks 12 and 24. Thus, the number of participants with a Better change in the severity score are reported in the table below.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. QBW251 450 mg arm was excluded from the analysis as it was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

The CASA-Q is a validated questionnaire instrument used to measure cough and sputum production, and their impact in patients COPD and/or chronic bronchitis. It contains a total of 20 items on a 5-step scale distributed in 4 domains: Cough symptoms, Cough impact, Sputum symptoms and Sputum impact. All items are rescored from 1-5 to 0-4 and then reverse scored such that better responses have higher scores. The four domains are ranged from 0-100 where higher scores associated with fewer symptoms/less impact due to cough or sputum.

Change from baseline in the CASA-Q cough and symptoms scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + run-in E-RS + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. QBW251 450 mg arm was excluded from the analysis as it was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

SGRQ measures health impairment and contains 50 items divided into three components: Symptoms, Activity and Impacts. A score was calculated for each component and a "Total" score was also calculated. In each case the lowest possible value is zero and the highest 100. Higher values correspond to greater impairment of quality of life.

Change from baseline in the SGRQ scores were analyzed using a Mixed Model for Repeated Measures (MMRM): treatment + baseline score + smoking status at screening + baseline SGRQ score + airflow limitation severity + region + time interval + treatment*time interval interaction + baseline score*time interval interaction.

The overall number of participants analyzed includes all randomized participants. The number analyzed per row represents participants with evaluable data at each time point. Results for the QBW251 450 mg arm need to be interpreted with caution as the arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

Venous whole blood samples were collected for pharmacokinetics characterization. Cmin was measured pre dose at all visits and was summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.

The overall number of participants analyzed includes the PK analysis set. The number analyzed per row represents participants with evaluable data at each time point. Results for the QBW251 450 mg arm need to be interpreted with caution as the arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. Cmax was measured in the samples taken at 3 hours post-dose with the exception of the participants included in the Serial PK set on Days 1 and 15 for whom all samples (1, 2, 4, 6, and 8 hours post-dose) were taken into consideration for the measurement of Cmax. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.

The overall number of participants analyzed includes the PK analysis set. The number analyzed per row represents participants with evaluable data at each time point. Results for the QBW251 450 mg arm need to be interpreted with caution as the arm was discontinued early based on a pre-defined pharmacokinetic exposure stopping rule.

Venous whole blood samples were collected for pharmacokinetics characterization. Cmax was calculated from plasma concentration data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.

The overall number of participants analyzed includes the Serial PK analysis set. The number analyzed per row represents participants with evaluable data at each time point.

Venous whole blood samples were collected for pharmacokinetics characterization. AUC0-24h was calculated from plasma concentration-time data using non-compartmental methods and summarized using descriptive statistics. All concentrations below the lower limit of quantification (LLOQ) were treated as zero.

The overall number of participants analyzed includes the Serial PK analysis set. The number analyzed per row represents participants with evaluable data at each time point.