Efficacy and Safety of Twice Daily 60mg AZD9668 in COPD for 12 Weeks in Patients on Background Budesonide/Formoterol

Study Overview
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Brief Summary
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The primary objective is to evaluate the efficacy of AZD9668 compared with placebo in symptomatic COPD patients by assessing the effects on lung function and symptoms of COPD

Official Title
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A 12-Week, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Multinational, Phase IIb Study to Evaluate the Efficacy and Safety of 60mg AZD9668 Administered Orally Twice Daily to Subjects With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Budesonide/Formoterol

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 >= 30 and < 80 % of predicted post-bronchodilator Symptomatic COPD for a total of 7 days in the two weeks prior to randomisation At least 1 COPD exacerbation from 4 weeks to 12 months before the screening visit Exclusion Criteria: Past history or current evidence of clinically significant heart disease Current diagnosis of asthma Patients who require long term oxygen therapy Worsening of COPD requiring treatment with antibiotics, 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: 40 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: 1<br> | Drug: AZD9668<br>* 2 x 30 mg oral tablets bd for 12 weeks<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* 2 x matched placebo to oral tablet bd for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline Pre-bronchodilator FEV1 (L) | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| End-value Pre-bronchodilator FEV1 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-bronchodilator FEV1 (L) - Baseline | Forced expiratory volume in 1 second (FEV1) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| Post-bronchodilator FEV1 (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Pre-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| Pre-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Post-bronchodilator FVC (L) - Baseline | Forced vital capacity (FVC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| Post-bronchodilator FVC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Baseline Pre-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| End-value Pre-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Baseline Post-bronchodilator FEV6 (L) | Forced expiratory volume in 6 seconds (FEV6) as a measure of lung function, measured post after bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| End-value Post-bronchodilator FEV6 (L) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Baseline Pre-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| End-value Pre-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Baseline Post-bronchodilator FEF25-75% (L/Sec) | Forced expiratory flow between 25% to 75% of vital capacity (FEF25-75%) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| End-value Post-bronchodilator FEF25-75% (L/Sec) | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Pre-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured before bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| Pre-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| Post-bronchodilator IC (L) - Baseline | Inspiratory capacity (IC) as a measure of lung function, measured after bronchodilator (salbutamol) use in the clinic. | Day 1 | 
| Post-bronchodilator IC (L) - End-value | End of treatment value - week 12 for completers, otherwise Last Observation Carried forward (LOCF) | up to week 12 | 
| PEF - Baseline Measured by Patient at Home (L/Min) in the Morning | Peak Expiratory Flow (L/min) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline | 
| PEF - End-value Measured by Patient at Home (L/Min) in the Morning | Peak expiratory flow (PEF) | Last 6 weeks on treatment | 
| FEV1 - Baseline Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) as a measure of lung function, measured at home by the patient each morning. Baseline is the mean of last 10 days of data before start of treatment. | Baseline | 
| FEV1 - End-value Measured by Patient at Home (L) in the Morning | Forced Expiratory Volume in 1 second (L) | Last 6 weeks on treatment | 
| EXACT - Baseline 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). Baseline is the mean of last 10 days of data before start of treatment. | Baseline | 
| EXACT - End-value 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). | Last 6 weeks on treatment | 
| BCSS - Baseline 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). Baseline is the mean of last 10 days of data before start of treatment. | Baseline | 
| BCSS - End-value 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). | Last 6 weeks on treatment | 
| Sputum Colour - Baseline | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). | Baseline | 
| Sputum Colour - End Value | Sputum Colour as assessed by the Bronkotest scale, reported on a scale from 1 - clear (best health status) to 5 - dark green (worst possible health status). End of treatment week 12 | End of treatment week 12 | 
| Use of Reliever Medication | Daily average of number of inhalations of reliever medication | Last 6 weeks on treatment | 
| Incremental Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 | 
| Incremental Shuttle Walk Test - End Value |  | Week 12 - visit 6 | 
| Endurance Shuttle Walk Test - Baseline | Endurance time (s) | Day 1 | 
| Endurance Shuttle Walk Test - End Value | Assessed at vist 6 -( last on treatment clinic visit) | Week 12 - visit 6 | 
| St George's Respiratory Questionnaire (COPD) - Overall Score at Baseline | 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)). | Day 1 | 
| St George's Respiratory Questionnaire (COPD) - End-value 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)).Questionaire assessed on vist 6 -( last on treatment clinic visit) | Measured Day 1 and 12 weeks | 
| Exacerbations - Clinic Defined | Number of patients having a clinic defined disease exacerbation. | Duration of the the treatment period - 12 weeks | 

 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