Trial in Non-cystic Fibrosis Bronchiectasis Patients With Chronic Lung Infections Treated With Colistimethate Sodium.

Time to First NCFB Pulmonary Exacerbation (PE) (days) = start date of first NCFB PE - date of randomization.

Subjects who completed or discontinued the trial with no NCFB PE are censored at the date of treatment completion/discontinuation.

The Saint George's Respiratory Questionnaire (SGRQ) is a validated 50-item symptom questionnaire developed to measure health status and Quality of Life (QoL) in subjects with obstructive airway diseases.

The scores range from 0 (best possible health status) to 100 (worst possible health status).

The total score is calculated as: (sum of the weights of the positive items of all domains / sum of the weights of all items of all domains)*100.

Change from Baseline was calculated as the SGRQ total score at the visit minus Baseline.

Change from baseline in SGRQ total score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate. An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The P. aeruginosa density as determined by the change in log10 CFU/mL sputum from baseline (Visit 2) to Day 28 (Visit 3) was compared between the treatment groups by an ANCOVA model including treatment, pooled site, i.e. country and use of stable concomitant therapy with oral macrolides as fixed effects and baseline value as covariate. Least square means in each treatment group, least square mean difference between treatments, their 95% CIs and associated p-value were estimated.

Summary statistics of the P. aeruginosa density (i.e. quantification, log10 CFU/mL sputum) and absolute change from baseline were provided by treatment group for each trial visit.

A severe pulmonary exacerbation was defined as requiring intravenous antibiotics and/or hospitalisation.

Time to First severe NCFB Pulmonary Exacerbation (PE) (days) = start date of first severe NCFB PE - date of randomization.

Subjects who completed or discontinued the trial with no severe NCFB PE are censored at the date of treatment completion/discontinuation.

Severe exacerbations are defined as those requiring IV antibiotics and/or hospitalisation.

Annualised number of exacerbation-free days = (follow-up time [days] - sum of durations of NCFB pulmonary exacerbations [days]) / follow-up time (years).

For NCFB pulmonary exacerbations with a resolution date after the treatment completion/discontinuation, the number of days of duration after the treatment completion/discontinuation will be subtracted from the sum of durations of NCFB pulmonary exacerbations.

Non-parametric ANCOVA model with a randomisation-based methodology was used. The model included treatment group, country, and use of stable concomitant therapy with oral macrolides as covariates.

Number of Days Work Absence is computed for each subject by summing all days of work absence.

Number of Days Work Absence per Employment Month = Number of Days of Work Absence / Overall Employment Time (months).

Number of Days Work Absence is computed for each subject by summing all days of work absence.

The number and percentage of subjects with at least one hospitalisation for a NCFB pulmonary exacerbation are provided. Percentages were computed on the total number of subjects with at least one pulmonary exacerbation.

The annual rate of hospitalisation for NCFB pulmonary exacerbation

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Physical Functioning Domain, the items 1, 2, 3, 4, 16 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Role Functioning Domain, the items 17, 20, 25, 27, 28 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Vitality Domain the items 6, 8, 9 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Emotional Functioning Domain the items 7, 10, 11, 23 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Social Functioning Domain the items 18, 19, 22, 26 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Treatment Burden Domain the items 12, 13, 14 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Health Perceptions Domain the items 5, 15, 21, 24 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.

The Quality of Life Bronchiectasis (QoL-B) is a validated self-administered, patient reported outcome measure assessing symptoms, functioning and health-related QoL for subjects with NCFB.

It contains 37 items in 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden).

Each QoL-B domain is assessed on a scale of 0 to 100, higher scores indicate better health status.

For the Respiratory Symptoms Domain the items from 29 to 37 are considered. Change from baseline in QoL-B domain score at Visit 3, Visit 4, Visit 5, Visit 6 and Visit 7 were analysed using a linear mixed model for repeated measures including treatment, visit, treatment-by-visit interaction, use of stable concomitant therapy with oral macrolides and pooled site, i.e. country, as fixed effects and baseline value as covariate.

An unstructured covariance matrix was assumed and the Kenward-Roger adjustment was used for the degrees of freedom.