Effect on Structural Changes in Airways, Measured by MSCT, of Twice Daily 60mg AZD9668 for 12 Weeks in Chronic Obstructive Pulmonary Disease (COPD) Patients

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate structural changes effected by AD9668 in the airways of adults with Chronic Obstructive Pulmonary Disease (COPD) by Multi-Slice Computed Tomography (MSCT)

Official Title
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A 12-week, Phase II, Double-blind, Placebo-Controlled, Randomised, Parallel-Group, Multi-Centre Study to Assess the Effect of 60mg AZD9668 Administered Orally Twice Daily on Structural Changes in the Airways by Multi-Slice Computed Tomography in Patients With Chronic Obstructive Pulmonary Disease.

Conditions
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Chronic Obstructive Pulmonary Disease (COPD)

Intervention / Treatment
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* Drug: AZD9668
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD with symptoms over 1 year FEV1/FVC < 70% and FEV1 >= 40 and < =70 % of predicted post-bronchodilator Ex-smokers for at least 12 months Exclusion Criteria: Past history or current evidence of clinically significant heart disease Current diagnosis of asthma Worsening of COPD requiring hospitalisation and/or treatment with antibiotics and/or an increase in inhaled steroid dose and/or oral steroids within 4 weeks of study visit 1b

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZD9668<br> | Drug: AZD9668<br>* 2 x 30 mg oral tablets twice daily (bid) for 12 weeks<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 2 x matched placebo to oral tablet twice daily (bid) for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AWT-Pi10 (Airway Wall Thickness of a Theoretical Airway With an Internal Perimeter of 10 mm) | AWT-Pi10 (mm) as a measure of structural changes in airways. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 5th Generation Wall Area Percentage | 5th Generation Wall Area Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Air Trapping Index (ATI) on Expiratory Scans | ATI Percentage as a measure of structural changes in airways. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Inspiratory Capacity (IC) | Inspiratory Capacity (L) as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Total Lung Capacity (TLC) | Total Lung Capacity (L) as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Functional Residual Capacity (FRC) | Functional Residual Capacity (L) as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Residual Volume (RV) | Residual volume (L) as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Specific Airway Conductance (SGaw) | Specific Airway Conductance as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Diffusion Capacity of Carbon Monoxide (DLco) | Capacity of Carbon Monoxide as a measure of lung function. End of treatment Least Squares Mean. | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Forced Vital Capacity (FVC) | Forced Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Post-bronchodilator Forced Vital Capacity (FVC) | Forced Vital Capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Pre-bronchodilator Slow Vital Capacity (SVC) | Slow Vital Capacity (L) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Post-bronchodilator Slow Vital Capacity (SVC) | Slow Vital capacity (L) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. End of treatment value or Last Observation Carried Forward (LOCF). | Measured after 12 weeks treatment (day 84) | 
| Peak Expiratory Flow (PEF) Morning (Daily Recordings) | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning. | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| Peak Expiratory Flow (PEF) Evening (Daily Recordings) | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each evening . | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| Forced Expiratory Volume in 1 Second (FEV1) Morning (Daily Recordings) | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning. | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| Forced Expiratory Volume in 1 Second (FEV1) Evening (Daily Recordings) | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each evening. | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| Breathlessness, Cough and Sputum Scale (BCSS) Total Score | Breathlessness, Cough and Sputum Scale, patient reported questionnaire as a measure of respiratory symptoms (reported on a 0 (best health status) to 12 (worst possible status) scale). | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| EXAcerbations of Chronic Pulmonary Disease Tool (EXACT) Total Score | EXAcerbations of Chronic pulmonary disease Tool, patient questionnaire as a measure of respiratory symptoms (reported as units on a 0 (best health status) to 100 (worst possible status) scale). | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Overall Score | St George's Respiratory Questionnaire for Chronic Obstructive Pulmonary Disease, as a measure of Quality of Life (reported on a % scale from 0 (best health status) to 100(worst possible status)). | Measured after 12 weeks treatment (day 84) | 
| Percentage of Reliever Free Days in Last Six Weeks of Treatment | Percentage of reliever free days in last 6 weeks on treatment. | Average from measurements recorded daily by patient in last 6 weeks of treatment. | 
| Exacerbations | Number of patients experiencing disease exacerbations on treatment. | Exacerbations were recorded at all study visits (after 1, 4, 8, and 12 weeks of treatment and at follow up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic, obstructive, pulmonary, lung, respiratory disease, efficacy, placebo-controlled, COPD, FEV1, St Georges Respiratory Questionnaire, Computed Tomography, MSCT