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

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 Cystic Fibrosis (CF) 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 Cystic Fibrosis

Conditions
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Cystic Fibrosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or post-menopausal or surgically sterile female patients Have a clinical diagnosis of Cystic Fibrosis with lung function tests greater or equal to 40% of normal Have normal renal function Exclusion Criteria: Lung transplant patients Significant liver disease Any other non-CF-related lung disease that may interfere with study assessments

Ages Eligible for Study
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Minimum Age: 16 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<br> | Drug: AZD9668<br>* 60 mg, oral tablet, twice daily for 28 days<br>|
| Placebo Comparator: Placebo<br> | Drug: AZD9668 Placebo equivalent<br>* Match placebo to 60 mg, 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 Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | Baseline and Values from day 21 to 28 | 
| Sputum Percentage Neutrophil Count | Percentage of neutrophils in white blood cell count.Change from Baseline (mean of 2 baseline visits) to the end of the treatment period (mean of 2 visits at the end of the treatment) | Baseline and Values from day 21 to 28 | 
| 24-hour Sputum Weight | Sputum weight (g) collected during 24 hour periods. 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 | 
| 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 Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%) | FEF25-75% (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 | 
| Morning Peak Expiratory Flow (PEF) | Morning Peak Expiratory Flow (L/min) as a measure of lung function.Change from 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 baseline value to mean of the last 7 days on treatment | The 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. | The last 7 days on treatment | 
| Cystic Fibrosis Questionnaire (CFQ-R) - Quittner | Cystic Fibrosis Questionnaire Overall Score as a measure of quality of life and disease symptoms. Scores range from 0 to 100, with higher scores indicating better health. The overall score is the sum of 12 subscores. Change from baseline to day 28. | Baseline and day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.Values from day 21 to 28 | 
| Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits. | 
| Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits | 
| Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits. | 
| Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits | 
| Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits | 
| Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline | Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits | End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 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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cystic fibrosis