A Study to Assess the Efficacy, Safety, and Tolerability of Brensocatib in Participants With Non-Cystic Fibrosis Bronchiectasis

PE was defined as having 3 or more of these symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis. A severe pulmonary exacerbation was that required intravenous (IV) antibacterial drug treatment and/or hospitalization. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil the protocol definition. The rate of PE was analyzed using the negative binomial model.

PE was defined as having 3 or more of following symptoms for at least 48 hours resulting in physician's decision to prescribe antibiotics:1.Increased cough2.Increased sputum volume or change in sputum consistency3.Increased sputum purulence4.Increased breathlessness &/or decreased exercise tolerance5.Fatigue &/or malaise6.Hemoptysis.Severe PE were those requiring IV antibacterial drug treatment &/or hospitalization. Minimum of 14 days must have occurred between one exacerbation onset and next. Any exacerbation that occurred within 14 days of prior exacerbation was not considered a new exacerbation. Time to first PE was calculated from randomization date to onset date of the first exacerbation. Participants who did not have exacerbation at end of 52-week treatment period were considered as censored at date of Week 52 in Cox proportional hazard model. Independent adjudication committee with pulmonary physicians adjudicated reported PE events to see if they fulfil protocol definition.

Responder status was based on percentage of participants who were exacerbation free over 52-weeks of treatment period. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee of pulmonary physicians adjudicated reported PE events to see if they fulfill protocol definition. For discontinuation prior to Week 52 without having experienced a confirmed PE, responder status was imputed by multiple imputation.

FEV1 was used to assess lung function and is the maximum amount of air that can be forced out in one second after first second after taking a forced expiration as measured by spirometer. Postbronchodilator FEV1 tests included spirometry tests performed referred to the spirometry performed within 30 minutes after administration of bronchodilator (4 puffs of salbutamol/albuterol, terbutaline or ipratropium). A positive change from baseline indicates an improvement in lung function. Baseline was the most recent non-missing assessment determined as best effort prior to the first dose of the investigational product.

Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics: 1. Increased cough 2. Increased sputum volume or change in sputum consistency 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis. A severe PE was defined as those requiring IV antibacterial drug treatment and/or hospitalization. A minimum of 14 days must have occurred between one exacerbation onset and the next. Any exacerbation that occurred less than 14 days from the prior exacerbation was not considered a new exacerbation. Independent adjudication committee with pulmonary physicians adjucated reported PE events to see if they fulfil the protocol definition. The rate of PE was analyzed using the negative binomial model.

The QOL-B is a validated, self-administered patient-reported outcome (PRO) that assesses symptoms, functioning, and health-related quality of life for participants with non-cystic fibrosis bronchiectasis (NCFBE). It contains 37 items in 8 domains (Respiratory Symptoms, Physical Functioning, Role Functioning, Emotional Functioning, Social Functioning, Vitality, Health Perceptions and Treatment Burden). Each of the 37 items is scored from 1 to 4, and each of the 8 domains scale scores is standardized on a 0-100 point scale, with higher scores representing fewer symptoms or better functioning. A positive change from Baseline indicates improvement in symptoms. For this outcome measure, change in the respiratory symptoms domain score from Baseline was reported. Baseline refers to most recent assessment on or before study Day 1.

An adverse event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are AEs that occurred on or after the date of first dose of study drugs and within 28 days after the end of treatment.