A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Cystic Fibrosis (INCA)
Primary Purpose
Cystic Fibrosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD9668
AZD9668 Placebo equivalent
Sponsored by
About this trial
This is an interventional basic science trial for Cystic Fibrosis focused on measuring cystic fibrosis
Eligibility Criteria
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
Sites / Locations
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AZD9668
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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
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)
24-hour Sputum Weight
Sputum weight (g) collected during 24 hour periods. Change from Baseline to 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.
Slow Vital Capacity (SVC)
Slow Vital capacity (L) as a measure of lung function. Change from Baseline to 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.
Forced Vital Capacity (FVC)
Forced Vital Capacity (L) as a measure of lung function. Change from Baseline to 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
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
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.
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.
Secondary Outcome Measures
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
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
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
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
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
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
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
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Ratio of day 28 to baseline
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00757848
Brief Title
A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Cystic Fibrosis
Acronym
INCA
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
August 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cystic Fibrosis
Keywords
cystic fibrosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
56 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AZD9668
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
AZD9668
Intervention Description
60 mg, oral tablet, twice daily for 28 days
Intervention Type
Drug
Intervention Name(s)
AZD9668 Placebo equivalent
Intervention Description
Match placebo to 60 mg, oral tablet, twice daily for 28 days
Primary Outcome Measure Information:
Title
Ratio of Sputum Absolute Neutrophil Count at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
Baseline and Values from day 21 to 28
Title
Sputum Percentage Neutrophil Count
Description
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)
Time Frame
Baseline and Values from day 21 to 28
Title
24-hour Sputum Weight
Description
Sputum weight (g) collected during 24 hour periods. Change from Baseline to day 28.
Time Frame
Baseline and day 28
Title
Forced Expiratory Volume in 1 Second (FEV1)
Description
Forced Expiratory Volume in 1 second (L) as a measure of lung function.Change from Baseline to day 28.
Time Frame
Baseline and day 28
Title
Slow Vital Capacity (SVC)
Description
Slow Vital capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame
Baseline and day 28
Title
Forced Expiratory Flow Between 25 and 75% of Forced Vital Capacity (FEF25-75%)
Description
FEF25-75% (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame
Baseline and day 28
Title
Forced Vital Capacity (FVC)
Description
Forced Vital Capacity (L) as a measure of lung function. Change from Baseline to day 28.
Time Frame
Baseline and day 28
Title
Morning Peak Expiratory Flow (PEF)
Description
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
Time Frame
Last 7 days on treatment
Title
Evening Peak Expiratory Flow (PEF)
Description
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
Time Frame
The last 7 days on treatment
Title
Bronkotest Diary Card Signs and Symptoms
Description
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.
Time Frame
The last 7 days on treatment
Title
Cystic Fibrosis Questionnaire (CFQ-R) - Quittner
Description
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.
Time Frame
Baseline and day 28
Secondary Outcome Measure Information:
Title
Ratio of Sputum Tumour Necrosis Factor Alpha (TNF α) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.Values from day 21 to 28
Title
Ratio of Sputum Interleukin 6 (IL-6) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Title
Ratio of Sputum Interleukin 1 Beta (IL-1β) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Title
Ratio of Sputum Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits.
Title
Ratio of Sputum Monocyte Chemoattractant Protein-1 (MCP-1) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Title
Ratio of Sputum Interleukin 8 (IL-8) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Title
Ratio of Sputum Leukotriene B4 (LTB4) at End of Treatment Compared to Baseline
Description
Ratio of the mean of 2 visits at the end of the treatment period to the mean of 2 baseline visits
Time Frame
End of treatment values from 2 visits (day 21 to 28) and baseline values from 2 visits
Title
Ratio of Urine Desmosine (Free) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description
Ratio of day 28 to baseline
Time Frame
Baseline and day 28
Title
Ratio of Urine Desmosine (Total) (Normalised for Creatinine) at End of Treatment Compared to Baseline
Description
Ratio of day 28 to baseline
Time Frame
Baseline and day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prof. Elborn
Organizational Affiliation
Belfast hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joanna Marks-Konczalik
Organizational Affiliation
AstraZeneca
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Kobenhavn
Country
Denmark
Facility Name
Research Site
City
Hamburg
Country
Germany
Facility Name
Research Site
City
Kiel
Country
Germany
Facility Name
Research Site
City
Leipzig
Country
Germany
Facility Name
Research Site
City
Munchen
Country
Germany
Facility Name
Research Site
City
Rabka-zdroj
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Moscow
Country
Russian Federation
Facility Name
Research Site
City
Goteborg
Country
Sweden
Facility Name
Research Site
City
Lund
Country
Sweden
Facility Name
Research Site
City
Stockholm
Country
Sweden
Facility Name
Research Site
City
Uppsala
Country
Sweden
Facility Name
Research Site
City
Belfast
State/Province
Northern Ireland
Country
United Kingdom
Facility Name
Research Site
City
Liverpool
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22267768
Citation
Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J. 2012 Oct;40(4):969-76. doi: 10.1183/09031936.00194611. Epub 2012 Jan 20.
Results Reference
derived
Learn more about this trial
A Phase II , Placebo-controlled Study to Assess Efficacy of 28 Day Oral AZD9668 in Patients With Cystic Fibrosis
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