A Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at Three Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium

Study Overview
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Brief Summary
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The primary objective is to evaluate the dose-response relationship and efficacy of AZD9668 at 3 dose levels compared with placebo in symptomatic COPD patients by assessing 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 Dose Range Finding Study to Evaluate the Efficacy and Safety of AZD9668 Administered Orally at 3 Dose Levels to Patients With Chronic Obstructive Pulmonary Disease (COPD) on Treatment With Tiotropium

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: AZD9668
* Drug: AZD9668
* Drug: AZD9668
* Drug: AZD9668 Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of COPD with symptoms over 1 year Smokers or ex-smokers Males or post-menopausal females between 40 and 80 years old Able to use electronic devices Exclusion Criteria: Past history or current evidence of clinically significant heart disease Current diagnosis of asthma Patients who require long term oxygen therapy Treatment with antibiotics 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>AZD9668 active treatment | Drug: AZD9668<br>* 2 x 30 mg oral tablets twice daily (bid) for 12 weeks<br>|
| Active Comparator: 2<br>AZD9668 active treatment | Drug: AZD9668<br>* 2 x 10 mg oral tablets twice daily (bid) for 12 weeks<br>|
| Active Comparator: 3<br>AZD9668 active treatment | Drug: AZD9668<br>* 2 x 2.5 mg oral tablets twice daily (bid) for 12 weeks<br>|
| Placebo Comparator: 4<br>AZD9668 placebo treatment | Drug: AZD9668 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 |
| --- | --- | --- |
| Baseline Pre-bronchodilator FEV1 (L) | Forced Expiratory Volume in 1 second (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-bronchodilator FEV1 (L) - Baseline | Forced Expiratory Volume in 1 second (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 
| Pre-bronchodilator FVC (L) - Baseline | Forced Vital Capacity (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 
| Post-bronchodilator FVC (L) - Baseline | Forced Vital Capacity (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 
| Pre-bronchodilator IC (L) - Baseline | Inspiratory Capacity (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 
| Post-bronchodilator IC (L) - Baseline | Inspiratory Capacity (L) 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) | Measured at clinic visits: 1, 4, 8 and 12 weeks | 
| 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 (L/min) | 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. | Measured daily in the evening for 12 weeks | 
| 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 | Measured daily in the evening for 12 weeks | 
| 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 | Measured at clinic visits:1, 4, 8 and 12 weeks | 
| Use of Reliever Medication | Daily average of number of inhalations of reliever medication | Last 6 weeks on treatment | 
| Six-minute Walk Test - Distance Walked at Baseline (m) |  | Day 1 | 
| Six-minute Walk Test - End-value Distance Walked (m) | distance walked on vist 6 - last on treatment clinic visit | Measured Day 1 and 12 weeks | 
| 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, Safety and tolerability, Placebo-controlled, Pharmacokinetics, COPD