Bronchiectasis
Conditions
Keywords
Bronchiectasis, QBW251, colony forming units
Brief summary
The purpose of this study is to determine whether potentiating the cystic fibrosis transmembrane conductance regulator (CFTR) with QBW251 in patients with bronchiectasis will demonstrate clinical safety and efficacy related to improved mucociliary clearance with reduced bacterial colonization as potential drivers of airway obstruction, reduced airway inflammation, exacerbations and mucus load, improved lung function, clinical symptoms and quality of life to support further development in bronchiectasis.
Detailed description
This was a randomized, participant- and investigator-blinded, placebo-controlled, parallel-group study investigating the preliminary efficacy and safety of QBW251 administered orally for 12 weeks in participants with bronchiectasis. Approximately 72 subjects were planned to be randomized in a 1:1 ratio to receive either QBW251 or placebo in order to achieve 60 subjects to complete the treatment period based on the assumption of a 16% drop-out rate. However, the study was prematurely terminated due to a Novartis strategic decision. As a result, only 42 participants were randomized to either the QBW251 300 mg b.i.d group or the placebo group. The study consisted of the screening, baseline/Day 1, treatment period, and end of study assessments (EOS) visit followed by an additional post-treatment safety follow up via phone call. The total duration for each patient in the study was up to approximately 19 weeks.
Interventions
DRUGQBW251
QBW251, 300 mg, oral use, one capsule, twice daily.
DRUGPlacebo
Matching placebo, 300 mg, oral use, one capsule, twice daily.
Sponsors
Innovative Medicines Initiative
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Male or female patients aged ≥18 years at screening. * Proven diagnosis of bronchiectasis by chest CT at screening as determined by investigator. * Evidence of sputum bacterial load of ≥106 CFU/mL with at least one potentially pathogenic microorganism (H. Influenzae, M catarrhalis, S aureus, S pneumoniae, Enterobacteriaceae, P aeruginosa, Stenotrophomonous maltophilia, or any potential pathogenic non-fermenting Gram-negative bacteria measured by dilution/outgrowth). * Documented history of at least one bronchiectasis exacerbation between January 2019 and study screening. * Patients with bronchial hypersecretion, defined as productive cough that occurred on most days (defined as \>50% days) for at least three consecutive months within 12 months prior to screening, as assessed by documentation of patient recollection (anamnesis) or documented in patients' record. * Patients were allowed to stay on fixed or free combinations of LABA/LAMA or LABA/ICS or LABA/LAMA/ICS as maintenance therapy if they were treated with them at a stable dose for the last 3 months prior to screening. Patients were also allowed to stay on macrolides as maintenance therapy if they were treated with them at a stable dose, 3 months before screening. Patients were allowed to use mucolytics or hyperosmolar agents if they were treated with them before study start. * If prescribed, patients were included in the study with unchanged chest physiotherapy for at least 4 weeks prior to screening. * Clinically stable pulmonary status in the opinion of the investigator and unlikely to require any change in the standard regimen of care during the course of the study.
Exclusion criteria
* Patients with a history of long-QT syndrome or the QTcF interval at screening and baseline was prolonged (QTcF \> 450 ms in males, \> 460 ms in females). * Patients with a history or current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure. A history of resolved Hepatitis A was not exclusionary. Patients with a prothrombin time international normalized ratio (PT/INR) of more than 1.5 × ULN at screening. Patients excluded for the PT/INR of more than 1.5 x ULN could be re-screened when the values returned to normal. * History of lung transplant or malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there was evidence of local recurrence or metastases. Patients with segmentectomy for other reasons than cancer were allowed to be included in the study. Patients with a history of cancer and 5 years or more disease free survival time might be included in the study by agreement with Novartis Medical Monitor on a case-by-case basis. * Patients requiring long-term oxygen therapy for chronic hypoxemia. This was typically patients requiring oxygen therapy \>12 h per day delivered by home oxygen cylinder or concentrator. Note: Nocturnal oxygen therapy for transient oxygen desaturations during sleep was allowed. * Patients with bronchiectasis who had a pulmonary exacerbation with a deterioration in three or more of the following key symptoms for at least 48 h: * cough; * sputum volume and/or consistency; * sputum purulence; * breathlessness and/or exercise tolerance; * fatigue and/or malaise; * hemoptysis And A clinician determined that a change in bronchiectasis treatment was required (e.g., requiring systemic glucocorticosteroid treatment and/or systemic or inhaled antibiotics) within 4 weeks prior to screening. In the event of an exacerbation occurring 4 weeks before screening, or between the screening and baseline (please see definition above), the participant was not to be enrolled. The participant might be rescreened once, 4 weeks after the resolution of exacerbation. * Participants with bronchiectasis requiring therapy that might interfere with the assessment of QBW251 efficiency or who were unlikely to respond to QBW251 as follows: * Participants with suspected active pulmonary tuberculosis or currently being treated for active pulmonary tuberculosis were not allowed. Note: Participants with a history of pulmonary tuberculosis could be enrolled if they met the following requirements: history of appropriate drug treatment followed by negative imaging results within 12 months prior to baseline visit suggesting low probability of recurrent active tuberculosis * Patients with active allergic bronchopulmonary aspergillosis and asthma as primary diagnosis. * Patients with cystic fibrosis * Current or ex-smokers with severe emphysema. * Participants with another concomitant pulmonary disease according to the definition of the International ERS/ATS guidelines, including but not limited to idiopathic pulmonary fibrosis (IPF), sarcoidosis or other granulomatous or infectious process. Concomitant COPD and asthma with characteristics of airway hyperresponsiveness as well as COPD-Asthma overlap syndrome were allowed as long as it was not the main, primary diagnosis in the opinion of the investigator. Primary ciliary dyskinesia (PCD) was allowed. * Participants currently receiving treatment for nontuberculous mycobacterial (NTM) pulmonary disease. If performed, patients with one or more positive cultures in the last 12 months for M. avium complex, M. abscessus complex, M. kansasii, M. malmoense, M. xenopi, M. simiae or M. chelonae, unless all subsequent NTM cultures (at least two) were negative and in the opinion of the investigator the patient did not met ATS criteria for NTM-pulmonary disease. * Patients receiving any medication that might influence the response to treatment within 4 weeks prior to screening including systemic or inhaled steroids (ICS alone), or other systemic immunomodulators, recombinant human DNAse, any systemic or inhaled antibiotics. * Patients with a body mass index (BMI) of more than 40 kg/m\^2
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12 | Baseline, 12 weeks | This measure reflects the amount of bacteria present in a patient's lungs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Baseline, Days 28, 56, 84 | The Quality of Life Questionnaire for Bronchiectasis (QOL-B) is a disease-specific questionnaire developed for non-cystic fibrosis bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension is scored separately on a scale of 0 to 100, and higher scores represent better outcomes. Only the respiratory symptoms domain score is reported for this outcome measure. |
| Change From Baseline in Fibrinogen Plasma Concentration | Baseline, 12 weeks | — |
| Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol) | Baseline, 12 weeks | The total number of puffs of rescue medication was divided by the total number of (full or half) days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient for the given visit interval. |
| Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Baseline, Days 28, 56, 84 | FEV1 is the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation. |
| Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Baseline, Days 28, 56, 84 | Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. |
| Change From Baseline in Bronchus Region Pi10 | Baseline, 12 weeks | Pi10 is the square root of the wall area for an idealized airway with a luminal perimeter of 10 mm. Pi10 is the most commonly used measure of wall thickening and represents a regional estimate of the small airways across the whole lung or a particular lobe. Measured by high resolution computed tomography (HRCT). |
| Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Baseline, 12 weeks | The region percent below or equal to -856 HU represents air trapping, which was evaluated by HRCT in the whole lung and in the regions (thirds, lobes). |
| Change From Baseline in Region Air Volume | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Average Inner Area | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Average Major Inner Diameter | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Average Minor Inner Diameter | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Average Outer Area | Baseline, 12 weeks | Measured by HRCT |
| Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum | Baseline, 12 weeks | — |
| Change From Baseline in Segment Average Wall Thickness | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Wall Area Percent | Baseline, 12 weeks | Measured by HRCT |
| Change From Baseline in Segment Wall Area | Baseline, 12 weeks | Measured by HRCT |
| Cmax of QBW251 | 1h, 2h, 3h, 4h, 6h and 8h post-dose on Days 1 and 28, and 3h post-dose on Day 56 and Day 84 | Maximum (peak) plasma concentration of QBW251 |
| Ctrough of QBW251 | Pre-dose Day 1, Day 28, Day 56, Day 84 | Trough (pre-dose) plasma concentration of QBW251 |
| Cmax of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | — |
| Ctrough of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | — |
| AUClast of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | Area under the concentration-time curve up to the last measurable concentration of QBW251 (AUClast) |
| Tmax of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | Time to reach maximum (peak) plasma concentration after single-dose administration |
| AUC0-12h of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | Twelve-hour AUC |
| Tlast of QBW251 for a Serial PK Set | Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28 | Tlast is the last measurable concentration sampling time. |
| Change From Baseline in Segment Average Wall Area Fraction | Baseline, 12 weeks | Wall area fraction or ratio was calculated by dividing the wall area of the corresponding segment to the total airway area. Measured by HRCT. |
Countries
China, Germany, Spain, United Kingdom
Participant flow
Pre-assignment details
All inclusion and exclusion criteria were checked at screening.
Participants by arm
| Arm | Count |
|---|---|
| QBW251 300 mg b.i.d Participants received QBW251 300 mg orally, twice daily (b.i.d.), for 12 weeks. | 21 |
| Placebo Participants received matching placebo, b.i.d., for 12 weeks. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | Total | QBW251 300 mg b.i.d |
|---|---|---|---|
| Age, Continuous | 56.2 years STANDARD_DEVIATION 12.96 | 54.5 years STANDARD_DEVIATION 14.38 | 52.8 years STANDARD_DEVIATION 15.8 |
| Race/Ethnicity, Customized Asian | 10 participants | 21 participants | 11 participants |
| Race/Ethnicity, Customized White | 11 participants | 21 participants | 10 participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 11 Participants | 21 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 | 0 / 42 |
| other Total, other adverse events | 14 / 21 | 13 / 21 | 27 / 42 |
| serious Total, serious adverse events | 2 / 21 | 0 / 21 | 2 / 42 |
Outcome results
Primary
Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12
This measure reflects the amount of bacteria present in a patient's lungs.
Time frame: Baseline, 12 weeks
Population: The Pharmacodynamics (PD) Analysis Set included all participants with available PD data at both baseline and at least one post-baseline assessment that were not affected by any protocol deviations. Results are reported for participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12 | -0.192 CFU/mL | Standard Deviation 1.4621 |
| Placebo | Change From Baseline In Bacterial Load Colony-forming Units of Potentially Pathogenic Microorganisms in Sputum at Week 12 | 0.340 CFU/mL | Standard Deviation 1.6476 |
Secondary
AUC0-12h of QBW251 for a Serial PK Set
Twelve-hour AUC
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | AUC0-12h of QBW251 for a Serial PK Set | Day 1 n=2 | 5260 h*ng/mL | Standard Deviation 1780 |
| QBW251 300 mg b.i.d | AUC0-12h of QBW251 for a Serial PK Set | Day 28 n=1 | 15400 h*ng/mL | — |
Secondary
AUClast of QBW251 for a Serial PK Set
Area under the concentration-time curve up to the last measurable concentration of QBW251 (AUClast)
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | AUClast of QBW251 for a Serial PK Set | Day 1 | 6100 h*ng/mL | Standard Deviation 2340 |
| QBW251 300 mg b.i.d | AUClast of QBW251 for a Serial PK Set | Day 28 | 10300 h*ng/mL | Standard Deviation 3100 |
Secondary
Change From Baseline in Bronchus Region Pi10
Pi10 is the square root of the wall area for an idealized airway with a luminal perimeter of 10 mm. Pi10 is the most commonly used measure of wall thickening and represents a regional estimate of the small airways across the whole lung or a particular lobe. Measured by high resolution computed tomography (HRCT).
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Bronchus Region Pi10 | Lung, Left, Superior Lobe, Apical Segment n=16,18 | -0.063 mm | Standard Deviation 0.414 |
| QBW251 300 mg b.i.d | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.074 mm | Standard Deviation 0.1867 |
| QBW251 300 mg b.i.d | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Inferior Lobe, Posterior Basal Segment n=14,18 | 0.001 mm | Standard Deviation 0.1999 |
| QBW251 300 mg b.i.d | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Superior Lobe, Apical Segment n=15,19 | -0.037 mm | Standard Deviation 0.199 |
| QBW251 300 mg b.i.d | Change From Baseline in Bronchus Region Pi10 | Lung, Left, Inferior Lobe, Posterior Basal Segment n=21,21 | -0.072 mm | Standard Deviation 0.3592 |
| Placebo | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Superior Lobe, Apical Segment n=15,19 | -0.026 mm | Standard Deviation 0.0991 |
| Placebo | Change From Baseline in Bronchus Region Pi10 | Lung, Left, Inferior Lobe, Posterior Basal Segment n=21,21 | -0.029 mm | Standard Deviation 1456 |
| Placebo | Change From Baseline in Bronchus Region Pi10 | Lung, Left, Superior Lobe, Apical Segment n=16,18 | 0.029 mm | Standard Deviation 0.16 |
| Placebo | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Inferior Lobe, Posterior Basal Segment n=14,18 | -0.015 mm | Standard Deviation 0.1071 |
| Placebo | Change From Baseline in Bronchus Region Pi10 | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.039 mm | Standard Deviation 0.1471 |
Secondary
Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol)
The total number of puffs of rescue medication was divided by the total number of (full or half) days with non-missing rescue data to derive the mean daily number of puffs of rescue medication taken for the patient for the given visit interval.
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol) | -0.37 number of puffs | Standard Deviation 1.069 |
| Placebo | Change From Baseline in Daily Rescue Medication Use (Salbutamol/Albuterol) | 0.14 number of puffs | Standard Deviation 0.895 |
Secondary
Change From Baseline in Fibrinogen Plasma Concentration
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Fibrinogen Plasma Concentration | -0.193 g/L | Standard Deviation 0.6278 |
| Placebo | Change From Baseline in Fibrinogen Plasma Concentration | -0.127 g/L | Standard Deviation 0.4828 |
Secondary
Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1)
FEV1 is the amount of air that can be forcibly exhaled from the lungs in the first second of a forced exhalation.
Time frame: Baseline, Days 28, 56, 84
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 28 n=20,20 | -0.002 liters | Standard Deviation 0.1113 |
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 56 n=18,18 | 0.031 liters | Standard Deviation 0.1086 |
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 84 n=17,19 | 0.045 liters | Standard Deviation 0.165 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 28 n=20,20 | 0.012 liters | Standard Deviation 0.1541 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 56 n=18,18 | 0.007 liters | Standard Deviation 0.1137 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Exploratory Volume in the First Second (FEV1) | Day 84 n=17,19 | 0.022 liters | Standard Deviation 0.126 |
Secondary
Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC)
Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible.
Time frame: Baseline, Days 28, 56, 84
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 28 n=20,20 | -0.068 liters | Standard Deviation 0.1834 |
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 56 n=18,18 | -0.019 liters | Standard Deviation 0.1943 |
| QBW251 300 mg b.i.d | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 84 n=17,19 | -0.019 liters | Standard Deviation 0.1779 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 28 n=20,20 | -0.017 liters | Standard Deviation 0.1685 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 56 n=18,18 | -0.049 liters | Standard Deviation 0.1358 |
| Placebo | Change From Baseline in Pre-bronchodilator Forced Vital Capacity (FVC) | Day 84 n=17,19 | 0.034 liters | Standard Deviation 0.2156 |
Secondary
Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain)
The Quality of Life Questionnaire for Bronchiectasis (QOL-B) is a disease-specific questionnaire developed for non-cystic fibrosis bronchiectasis. It covers 8 dimensions: physical functioning, role functioning, emotional functioning, social functioning, vitality, treatment burden, health perceptions, and respiratory symptoms. Each dimension is scored separately on a scale of 0 to 100, and higher scores represent better outcomes. Only the respiratory symptoms domain score is reported for this outcome measure.
Time frame: Baseline, Days 28, 56, 84
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 28 n=12,19 | 5.247 score on a scale | Standard Deviation 10.9936 |
| QBW251 300 mg b.i.d | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 56 n=12,20 | 1.852 score on a scale | Standard Deviation 5.8026 |
| QBW251 300 mg b.i.d | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 84 n=13,20 | 2.849 score on a scale | Standard Deviation 9.4612 |
| Placebo | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 28 n=12,19 | 7.212 score on a scale | Standard Deviation 9.5209 |
| Placebo | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 56 n=12,20 | 1.852 score on a scale | Standard Deviation 11.7429 |
| Placebo | Change From Baseline in Quality of Life Questionnaire for Bronchiectasis (QOL-B) (Respiratory Symptoms Domain) | Day 84 n=13,20 | 3.519 score on a scale | Standard Deviation 11.9848 |
Secondary
Change From Baseline in Region Air Volume
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung n=16,19 | 7.588 liters | Standard Deviation 362.231 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Left n=16,19 | 6.719 liters | Standard Deviation 188.304 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Left Lower Lobe n=15,19 | 22.142 liters | Standard Deviation 125.643 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Left Upper Lobe n=16,19 | -14.039 liters | Standard Deviation 82.95 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Right n=16,19 | 0.869 liters | Standard Deviation 179.912 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Right Lower Lobe n=16,19 | 9.886 liters | Standard Deviation 95.0629 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Right Middle Lobe n=16,19 | -3.233 liters | Standard Deviation 20.4193 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Lung, Right Upper Lobe n=16,19 | -5.784 liters | Standard Deviation 78.3195 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Left Lower n=16,19 | -3.409 liters | Standard Deviation 82.0621 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Left Middle n=16,19 | -1.319 liters | Standard Deviation 76.6437 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Left Upper n=16,19 | 11.444 liters | Standard Deviation 73.0426 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Right Lower n=16,19 | -20.490 liters | Standard Deviation 122.493 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Right Middle n=16,19 | 8.762 liters | Standard Deviation 98.3416 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Air Volume | Thirds, Right Upper n=16,19 | 12.574 liters | Standard Deviation 84.6939 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Left Upper n=16,19 | -0.432 liters | Standard Deviation 41.7288 |
| Placebo | Change From Baseline in Region Air Volume | Lung n=16,19 | -4.667 liters | Standard Deviation 323.292 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Right Upper Lobe n=16,19 | 6.830 liters | Standard Deviation 81.4095 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Left n=16,19 | -7.304 liters | Standard Deviation 144.047 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Right Middle n=16,19 | 2.994 liters | Standard Deviation 93.2434 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Left Lower Lobe n=15,19 | -14.848 liters | Standard Deviation 84.4328 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Left Lower n=16,19 | -5.155 liters | Standard Deviation 50.2945 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Left Upper Lobe n=16,19 | 7.545 liters | Standard Deviation 69.1768 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Right Lower n=16,19 | -7.548 liters | Standard Deviation 76.9902 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Right n=16,19 | 2.637 liters | Standard Deviation 190.892 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Left Middle n=16,19 | -1.992 liters | Standard Deviation 63.8795 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Right Lower Lobe n=16,19 | -5.435 liters | Standard Deviation 105.079 |
| Placebo | Change From Baseline in Region Air Volume | Thirds, Right Upper n=16,19 | 5.327 liters | Standard Deviation 60.5143 |
| Placebo | Change From Baseline in Region Air Volume | Lung, Right Middle Lobe n=16,19 | 1.242 liters | Standard Deviation 13.5834 |
Secondary
Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU)
The region percent below or equal to -856 HU represents air trapping, which was evaluated by HRCT in the whole lung and in the regions (thirds, lobes).
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung n=15,17 | -0.284 percent of region | Standard Deviation 9.2755 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left n=15,17 | -1.659 percent of region | Standard Deviation 8.5613 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left Lower Lobe n=15,17 | -3.582 percent of region | Standard Deviation 8.4976 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left Upper Lobe n=15,17 | 0.002 percent of region | Standard Deviation 10.3698 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right n=15,17 | 1.410 percent of region | Standard Deviation 10.8421 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Lower Lobe n=15,17 | 0.303 percent of region | Standard Deviation 7.9933 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Middle Lobe n=15,17 | 2.877 percent of region | Standard Deviation 10.3635 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Upper Lobe n=15,17 | 1.513 percent of region | Standard Deviation 13.1404 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Lower n=15,17 | -2.726 percent of region | Standard Deviation 9.4063 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Middle n=15,17 | -2.319 percent of region | Standard Deviation 8.3145 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Upper n=15,17 | 0.940 percent of region | Standard Deviation 10.8083 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Lower n=15,17 | 0.394 percent of region | Standard Deviation 9.2444 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Middle n=15,17 | 1.563 percent of region | Standard Deviation 11.7119 |
| QBW251 300 mg b.i.d | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Upper n=15,17 | 1.905 percent of region | Standard Deviation 12.7615 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Upper n=15,17 | -1.056 percent of region | Standard Deviation 9.7966 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung n=15,17 | -1.074 percent of region | Standard Deviation 8.7794 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Upper Lobe n=15,17 | -2.105 percent of region | Standard Deviation 11.4788 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left n=15,17 | -1.095 percent of region | Standard Deviation 7.22 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Middle n=15,17 | -0.804 percent of region | Standard Deviation 10.4909 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left Lower Lobe n=15,17 | -2.975 percent of region | Standard Deviation 7.8007 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Lower n=15,17 | -1.109 percent of region | Standard Deviation 4.8754 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Left Upper Lobe n=15,17 | 1.946 percent of region | Standard Deviation 10.7307 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Lower n=15,17 | -2.214 percent of region | Standard Deviation 9.6626 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right n=15,17 | -1.552 percent of region | Standard Deviation 10.1631 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Left Middle n=15,17 | -0.892 percent of region | Standard Deviation 8.0664 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Lower Lobe n=15,17 | -2.193 percent of region | Standard Deviation 10.7784 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Thirds, Right Upper n=15,17 | -2.052 percent of region | Standard Deviation 11.7677 |
| Placebo | Change From Baseline in Region Percent Below or Equal to -856 Hounsfield Units (HU) | Lung, Right Middle Lobe n=15,17 | 0.502 percent of region | Standard Deviation 9.3885 |
Secondary
Change From Baseline in Segment Average Inner Area
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lower Lobe Bronchus, Left n=15,17 | 2.009 mm^2 | Standard Deviation 10.4977 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lung, Left Upper Lobe n=15,18 | 1.106 mm^2 | Standard Deviation 11.1387 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lung, Right Lower Lobe n=16,19 | -0.677 mm^2 | Standard Deviation 7.9904 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lung, Right Upper Lobe n=16,19 | 0.667 mm^2 | Standard Deviation 4.995 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.138 mm^2 | Standard Deviation 4.8198 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Inner Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | -0.502 mm^2 | Standard Deviation 5.2215 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.379 mm^2 | Standard Deviation 2.8929 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lower Lobe Bronchus, Left n=15,17 | -1.376 mm^2 | Standard Deviation 6.541 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lung, Right Upper Lobe n=16,19 | -2.653 mm^2 | Standard Deviation 14.9922 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lung, Left Upper Lobe n=15,18 | 1.506 mm^2 | Standard Deviation 7.5668 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 1.828 mm^2 | Standard Deviation 5.5992 |
| Placebo | Change From Baseline in Segment Average Inner Area | Lung, Right Lower Lobe n=16,19 | -2.119 mm^2 | Standard Deviation 6.7263 |
Secondary
Change From Baseline in Segment Average Major Inner Diameter
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lower Lobe Bronchus, Left n=15,17 | 0.364 mm | Standard Deviation 1.0234 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lung, Left Upper Lobe n=15,18 | -0.095 mm | Standard Deviation 0.7972 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right Lower Lobe n=16,19 | -0.040 mm | Standard Deviation 0.7883 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right Upper Lobe n=16,19 | 0.081 mm | Standard Deviation 0.7149 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.075 mm | Standard Deviation 0.9001 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.046 mm | Standard Deviation 0.8759 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.066 mm | Standard Deviation 0.5419 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lower Lobe Bronchus, Left n=15,17 | -0.128 mm | Standard Deviation 0.5242 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right Upper Lobe n=16,19 | -0.525 mm | Standard Deviation 1.969 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lung, Left Upper Lobe n=15,18 | -0.116 mm | Standard Deviation 0.7192 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.336 mm | Standard Deviation 1.2354 |
| Placebo | Change From Baseline in Segment Average Major Inner Diameter | Lung, Right Lower Lobe n=16,19 | -0.207 mm | Standard Deviation 0.7876 |
Secondary
Change From Baseline in Segment Average Minor Inner Diameter
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lower Lobe Bronchus, Left n=15,17 | 0.080 mm | Standard Deviation 0.81 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Left Upper Lobe n=15,18 | 0.160 mm | Standard Deviation 0.7449 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right Upper Lobe n=16,19 | 0.034 mm | Standard Deviation 0.4546 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.037 mm | Standard Deviation 0.5225 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right, Middle Lobe, Medial Segment n=16,19 | -0.309 mm | Standard Deviation 0.7621 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right Lower Lobe n=16,19 | -0.011 mm | Standard Deviation 0.6186 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right Upper Lobe n=16,19 | 0.127 mm | Standard Deviation 0.5699 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lower Lobe Bronchus, Left n=15,17 | -0.204 mm | Standard Deviation 0.7995 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.065 mm | Standard Deviation 0.5016 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Left Upper Lobe n=15,18 | 0.120 mm | Standard Deviation 0.5935 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right Lower Lobe n=16,19 | -0.220 mm | Standard Deviation 0.6556 |
| Placebo | Change From Baseline in Segment Average Minor Inner Diameter | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.058 mm | Standard Deviation 0.4702 |
Secondary
Change From Baseline in Segment Average Outer Area
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lower Lobe Bronchus, Left n=15,17 | 3.805 mm^2 | Standard Deviation 15.3509 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lung, Left Upper Lobe n=15,18 | 2.527 mm^2 | Standard Deviation 25.2783 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lung, Right Lower Lobe n=16,19 | -0.887 mm^2 | Standard Deviation 13.2296 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lung, Right Upper Lobe n=16,19 | 3.054 mm^2 | Standard Deviation 11.6503 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.011 mm^2 | Standard Deviation 8.9779 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Outer Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | -1.929 mm^2 | Standard Deviation 12.3065 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.574 mm^2 | Standard Deviation 6.6601 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lower Lobe Bronchus, Left n=15,17 | -3.575 mm^2 | Standard Deviation 9.6603 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lung, Right Upper Lobe n=16,19 | -6.171 mm^2 | Standard Deviation 35.7465 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lung, Left Upper Lobe n=15,18 | 6.387 mm^2 | Standard Deviation 15.1487 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 3.655 mm^2 | Standard Deviation 9.0492 |
| Placebo | Change From Baseline in Segment Average Outer Area | Lung, Right Lower Lobe n=16,19 | -2.439 mm^2 | Standard Deviation 10.4313 |
Secondary
Change From Baseline in Segment Average Wall Area Fraction
Wall area fraction or ratio was calculated by dividing the wall area of the corresponding segment to the total airway area. Measured by HRCT.
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lower Lobe Bronchus, Left n=15,17 | -0.009 ratio | Standard Deviation 0.0515 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lung, Left Upper Lobe n=15,18 | 0.002 ratio | Standard Deviation 0.0553 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right Lower Lobe n=16,19 | 0.001 ratio | Standard Deviation 0.0377 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right Upper Lobe n=16,19 | 0.007 ratio | Standard Deviation 0.0392 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.002 ratio | Standard Deviation 0.0414 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.007 ratio | Standard Deviation 0.0281 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.006 ratio | Standard Deviation 0.0262 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lower Lobe Bronchus, Left n=15,17 | -0.002 ratio | Standard Deviation 0.031 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right Upper Lobe n=16,19 | 0.001 ratio | Standard Deviation 0.0347 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lung, Left Upper Lobe n=15,18 | 0.013 ratio | Standard Deviation 0.0436 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.002 ratio | Standard Deviation 0.0347 |
| Placebo | Change From Baseline in Segment Average Wall Area Fraction | Lung, Right Lower Lobe n=16,19 | 0.011 ratio | Standard Deviation 0.0277 |
Secondary
Change From Baseline in Segment Average Wall Thickness
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lower Lobe Bronchus, Left n=15,17 | 0.001 mm | Standard Deviation 0.168 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lung, Left Upper Lobe n=15,18 | 0.014 mm | Standard Deviation 0.3422 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lung, Right Lower Lobe n=16,19 | 0.001 mm | Standard Deviation 0.1691 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lung, Right, Middle Lobe, Medial Segment n=16,19 | -0.040 mm | Standard Deviation 0.1606 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lung, Right Upper Lobe n=16,19 | 0.054 mm | Standard Deviation 0.2231 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Average Wall Thickness | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.014 mm | Standard Deviation 0.0828 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.004 mm | Standard Deviation 0.0968 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lower Lobe Bronchus, Left n=15,17 | -0.042 mm | Standard Deviation 0.0987 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lung, Right Upper Lobe n=16,19 | -0.030 mm | Standard Deviation 0.2941 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lung, Left Upper Lobe n=15,18 | 0.081 mm | Standard Deviation 0.2417 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.057 mm | Standard Deviation 0.0766 |
| Placebo | Change From Baseline in Segment Average Wall Thickness | Lung, Right Lower Lobe n=16,19 | 0.021 mm | Standard Deviation 0.09 |
Secondary
Change From Baseline in Segment Wall Area
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lower Lobe Bronchus, Left n=15,17 | 1.796 mm^2 | Standard Deviation 6.6301 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lung, Left Upper Lobe n=15,18 | 1.421 mm^2 | Standard Deviation 18.5698 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lung, Right Lower Lobe n=16,19 | -0.209 mm^2 | Standard Deviation 6.973 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lung, Right Upper Lobe n=16,19 | 2.388 mm^2 | Standard Deviation 9.7223 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.127 mm^2 | Standard Deviation 4.6312 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | -1.427 mm^2 | Standard Deviation 7.3051 |
| Placebo | Change From Baseline in Segment Wall Area | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.194 mm^2 | Standard Deviation 4.0452 |
| Placebo | Change From Baseline in Segment Wall Area | Lower Lobe Bronchus, Left n=15,17 | -2.199 mm^2 | Standard Deviation 4.3938 |
| Placebo | Change From Baseline in Segment Wall Area | Lung, Right Upper Lobe n=16,19 | -3.518 mm^2 | Standard Deviation 21.8864 |
| Placebo | Change From Baseline in Segment Wall Area | Lung, Left Upper Lobe n=15,18 | 4.881 mm^2 | Standard Deviation 12.438 |
| Placebo | Change From Baseline in Segment Wall Area | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 1.827 mm^2 | Standard Deviation 3.8885 |
| Placebo | Change From Baseline in Segment Wall Area | Lung, Right Lower Lobe n=16,19 | -0.320 mm^2 | Standard Deviation 4.5446 |
Secondary
Change From Baseline in Segment Wall Area Percent
Measured by HRCT
Time frame: Baseline, 12 weeks
Population: PD Analysis Set. Results are reported for participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lower Lobe Bronchus, Left n=15,17 | -0.009 percent | Standard Deviation 0.0515 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lung, Left Upper Lobe n=15,18 | 0.002 percent | Standard Deviation 0.0553 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lung, Right Lower Lobe n=16,19 | 0.001 percent | Standard Deviation 0.0376 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lung, Right Upper Lobe n=16,19 | 0.007 percent | Standard Deviation 0.0394 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | -0.003 percent | Standard Deviation 0.0411 |
| QBW251 300 mg b.i.d | Change From Baseline in Segment Wall Area Percent | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.007 percent | Standard Deviation 0.0282 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lung, Right, Middle Lobe, Lateral Segment n=16,19 | 0.006 percent | Standard Deviation 0.0261 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lower Lobe Bronchus, Left n=15,17 | -0.002 percent | Standard Deviation 0.0305 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lung, Right Upper Lobe n=16,19 | 0.002 percent | Standard Deviation 0.0337 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lung, Left Upper Lobe n=15,18 | 0.013 percent | Standard Deviation 0.0437 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lung, Right, Middle Lobe, Medial Segment n=16,19 | 0.002 percent | Standard Deviation 0.0347 |
| Placebo | Change From Baseline in Segment Wall Area Percent | Lung, Right Lower Lobe n=16,19 | 0.011 percent | Standard Deviation 0.0276 |
Secondary
Cmax of QBW251
Maximum (peak) plasma concentration of QBW251
Time frame: 1h, 2h, 3h, 4h, 6h and 8h post-dose on Days 1 and 28, and 3h post-dose on Day 56 and Day 84
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Cmax of QBW251 | Day 1 n=19 | 1120 ng/mL | Standard Deviation 913 |
| QBW251 300 mg b.i.d | Cmax of QBW251 | Day 28 n=19 | 1520 ng/mL | Standard Deviation 951 |
| QBW251 300 mg b.i.d | Cmax of QBW251 | Day 56 n=19 | 1190 ng/mL | Standard Deviation 578 |
| QBW251 300 mg b.i.d | Cmax of QBW251 | Day 84 n=18 | 1460 ng/mL | Standard Deviation 947 |
Secondary
Cmax of QBW251 for a Serial PK Set
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Cmax of QBW251 for a Serial PK Set | Day 1 | 2470 ng/mL | Standard Deviation 787 |
| QBW251 300 mg b.i.d | Cmax of QBW251 for a Serial PK Set | Day 28 | 3000 ng/mL | Standard Deviation 1390 |
Secondary
Ctrough of QBW251
Trough (pre-dose) plasma concentration of QBW251
Time frame: Pre-dose Day 1, Day 28, Day 56, Day 84
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Ctrough of QBW251 | Day 1 n=21 | 0.00 ng/mL | Standard Deviation 0 |
| QBW251 300 mg b.i.d | Ctrough of QBW251 | Day 28 n=20 | 489 ng/mL | Standard Deviation 371 |
| QBW251 300 mg b.i.d | Ctrough of QBW251 | Day 56 n=19 | 483 ng/mL | Standard Deviation 395 |
| QBW251 300 mg b.i.d | Ctrough of QBW251 | Day 84 n=18 | 498 ng/mL | Standard Deviation 416 |
Secondary
Ctrough of QBW251 for a Serial PK Set
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Ctrough of QBW251 for a Serial PK Set | Day 1 | 0.00 ng/mL | Standard Deviation 0 |
| QBW251 300 mg b.i.d | Ctrough of QBW251 for a Serial PK Set | Day 28 | 603 ng/mL | Standard Deviation 142 |
Secondary
Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum
Time frame: Baseline, 12 weeks
Population: PD Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| QBW251 300 mg b.i.d | Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum | 0 Participants |
| Placebo | Number of Participants With Absence of Any Colony-forming Units of Potentially Pathogenic Bacteria Sputum | 0 Participants |
Secondary
Tlast of QBW251 for a Serial PK Set
Tlast is the last measurable concentration sampling time.
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| QBW251 300 mg b.i.d | Tlast of QBW251 for a Serial PK Set | Day 1 | 7.99 hours | Standard Deviation 0.00962 |
| QBW251 300 mg b.i.d | Tlast of QBW251 for a Serial PK Set | Day 28 | 8.00 hours | Standard Deviation 0 |
Secondary
Tmax of QBW251 for a Serial PK Set
Time to reach maximum (peak) plasma concentration after single-dose administration
Time frame: Pre-dose, 1h, 2h, 3h, 4h, 6h and 8h post-dose on Day 1 and Day 28
Population: The pharmacokinetic (PK) analysis set included all participants with at least one available valid PK concentration measurement, who received any dose of QBW251 and had no protocol deviations that affected PK data. Results data were collected for a subset of participants at selected sites. PK parameters were only analyzed in the QBW251 arm.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| QBW251 300 mg b.i.d | Tmax of QBW251 for a Serial PK Set | Day 1 | 1.00 hours |
| QBW251 300 mg b.i.d | Tmax of QBW251 for a Serial PK Set | Day 28 | 2.00 hours |