A Safety, Tolerability and Efficacy Study With QBW251 in COPD Patients With QBW251

Study Overview
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Brief Summary
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To evaluate the efficacy, safety and tolerability of multiple doses of QBW251 vs placebo administered orally, on airway function, lung volume, and quality of life in patients with chronic obstructive pulmonary disease (COPD)

Official Title
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A Randomized, Double Blind, Placebo Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of Multiple Doses of QBW251 in Patients With COPD

Conditions
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Chronic Obstructive Pulmonary Disease, COPD

Intervention / Treatment
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* Drug: QBW251
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a diagnosis of GOLD II-III chronic obstructive pulmonary disease (COPD); Must have clinical diagnosis of chronic bronchitis; Must be either a current smoker (smoked ≤ 1 pack per day on average for the last 3 months with at least a 10 pack year smoking history) OR an ex-smoker with at least a 10 pack year smoking history; Exclusion Criteria: Must not be receiving chronic, daily, systemic steroids; Must not have severe emphysema (determined by HRCT); Must not have had a COPD exacerbation or respiratory tract infection requiring antibiotics or oral steroids or hospitalization within 6 weeks of screening; Must not be pregnant or nursing or a woman of child bearing potential; Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: QBW251<br>QBW251 will be provided to participants during 70 days | Drug: QBW251<br>* QBW251 capsule(s) taken orally twice per day<br>|
| Placebo Comparator: Placebo<br>Placebo will be provided to participants during 70 days | Drug: Placebo<br>* Matching placebo capsule(s) taken orally twice per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Lung Clearance Index (LCI) | Change from baseline to Day 29 in LCI as measured by multiple breath nitrogen washout (MBNW) technique. MBNW is the time taken to wash out nitrogen while breathing 100% oxygen. | Baseline and Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in FEV1 Pre-bronchodilator | Change From Baseline to Day 29 in FEV1 will be measured by spirometer before bronchodilator administration. Forced Expiratory Volume in 1 Second (FEV1) is the amount of air that can be exhaled in 1 second. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. | Day 29 | 
| Change From Baseline in FEV1 Post-bronchodilator | Change From Baseline to Day 29 in FEV1 will be measured by spirometer after bronchodilator administration. Forced Expiratory Volume in 1 Second (FEV1) is the amount of air that can be exhaled in 1 second. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. | Day 29 | 
| Change From Baseline in FVC Pre Bronchodilator | Change From Baseline to Day 29 in FVC will be measured by spirometer before bronchodilator administration. Forced Vital Capacity (FVC) is the maximum amount of air a person can expel from the lungs after a maximum inhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator | Day 29 | 
| Change From Baseline in FVC Post- Bronchodilator | Change From Baseline to Day 29 in FVC will be measured by spirometer after bronchodilator administration. Forced Vital Capacity (FVC) is the maximum amount of air a person can expel from the lungs after a maximum inhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator | Day 29 | 
| Change From Baseline in TLC | Change From Baseline to Day 29 in TLC will be measured by spirometry. Total lung capacity (TLC) is the volume in the lungs at maximal inflation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. | Day 29 | 
| Change From Baseline in RV | Change From Baseline to Day 29 in RV will be measured by spirometry. Residual volume (RV) is the volume of air remaining in the lungs after a maximal exhalation. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. | Day 29 | 
| Change From Baseline in FRC | Change From Baseline to Day 29 in FRC will be measured by spirometry. Functional residual capacity (FRC) is the volume in the lungs at the end-expiratory position. All spirometry calibrations and evaluations will follow the recommendations of the American Thoracic Society / European Respiratory Society guidelines for acceptability. | Day 29 | 
| Change From Baseline in DLCO | Diffusing capacity of the lung for carbon monoxide (DLCO) is the extent to which oxygen passes from the lung to the blood. | Day 29 | 
| Plasma Concentration of QBW251 by TMax (0-8hours) | Tmax is the time to reach the maximum concentration after drug administration. | Day 1, Day 28 | 
| Plasma Concentration of QBW251 by CMax (0-8hours) | Cmax is the observed maximum plasma concentration following drug administration. | Day 1, Day 28 | 
| Plasma Concentration of QBW251 by AUClast (0-8hours) | AUClast is the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration. | Day 1, Day 28 | 
| Plasma Concentration of QBW251 by AUC0-12h | AUC 0-12h is the area under the plasma concentration-time curve from time zero to 12 hours. | Day 1, Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic bronchitis,, inflammation,, airway,, LCI,, COPD,, pulmonary function test,, lung function,, controlled clinical trial,, randomized,, smoker, airflow,