A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Bronchiectasis

Study Overview
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Brief Summary
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The purpose of this study is to investigate if treatment with AZD9668 for 28 days is effective in treating Bronchiectasis (Brx) and if so how it compares to placebo (a substance which does not have any action).

Official Title
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A Phase II, Randomised, Double-blind, Placebo-controlled, Parallel Group Study to Assess the Efficacy of 28 Day Oral Administration of AZD9668 in Patients With Bronchiectasis

Conditions
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Bronchiectasis

Intervention / Treatment
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* Drug: AZD9668
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female of non child bearing potential Clinical diagnosis of bronchiectasis Be sputum producers, with history of chronic expectoration on most days Exclusion Criteria: Concomitant diagnosis of pulmonary disease other than bronchiectasis or COPD FEV1 of <30% of predicted normal

Ages Eligible for Study
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Minimum Age: 18 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 |
| --- | --- |
| Experimental: AZD9668 active treatment<br> | Drug: AZD9668<br>* 2 x 30 mg, oral tablet, twice daily for 28 days<br>|
| Placebo Comparator: AZD9668 placebo treatment<br> | Drug: Placebo<br>* 2 x Matched placebo, oral tablet, twice daily for 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Absolute Neutrophil Count at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of the Percentage Neutrophil Count at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| 24-hour Sputum Weight(g) | Sputum weight (g) collected during 24 hour periods.Change from Baseline to day 28 | Baseline and day 28 | 
| Slow Vital Capacity (SVC) | Slow Vital Capacity (L) as a measure of lung function.Change from baseline to day 28 | Baseline and day 28 | 
| Forced Expiratory Volume in 1 Second (FEV1) | Forced Expiratory Volume in 1 Second (L) as a measure of lung function.Change from baseline to day 28 | Baseline and day 28 | 
| Forced Vital Capacity (FVC) | Forced Vital Capacity (L) as a measure of lung function.Change from baseline to day 28 | Baseline and day 28 | 
| Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | FEF25-75% as a measure of lung function.Change from baseline to day 28 | Baseline and day 28 | 
| Morning Peak Expiratory Flow (PEF) | Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment | Last 7 days on treatment | 
| Evening Peak Expiratory Flow (PEF) | Evening Peak Expiratory Flow (L/min) as a measure of lung function.Change from mean baseline value to mean of the last 7 days on treatment | Last 7 days on treatment | 
| Bronkotest Diary Card Signs and Symptoms | The Bronkotest diary card includes 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). ANOVA models were fitted to compare the change from baseline between AZD9668 and placebo for each question separately, with a p-value of 0.1 considered statistically significant. The number of number of these 8 measures with significant differences is reported. | Last 7 days on treatment | 
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) | SGRQ total score shows the impact of COPD on patient's health status, and expressed as a percentage of impairment with scale from 0 (best health status) to 100 (worst possible status). Change from baseline to day 28. | Baseline and day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits | End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. | 
| Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline | Ratio of day 28 to baseline | Baseline and day 28 | 
| Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline | Ratio of day 28 to baseline | Baseline and day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bronchiectasis, Phase II