Back to resultsEvaluation of the Effect of AZD5069 in Patients With Bronchiectasis (STRATUS)
Primary Purpose
Bronchiectasis, Lung Disease, Respiratory Diseases
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
AZD5069
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bronchiectasis focused on measuring Bronchiectasis, Neutrophil, Respiratory disease, Sputum
Eligibility Criteria
Inclusion Criteria:
- Male, or female of non-child bearing potential; ie, women who are permanently or surgically sterilised or post-menopausal.
- Aged 18 to 80 years inclusive at screening (Visit 1)
- Have a clinical diagnosis of idiopathic or post infective bronchiectasis as diagnosed with a historical high resolution computerised tomography (HRCT) or bronchogram
- Be sputum producers with a history of chronic expectoration on most days of most weeks of the year. Patients should have a history of spontaneously producing sputum on a daily basis and should be able to provide at least 2 of the 3 required baseline sputum samples with an average of 3 mL or more.
- Be on a stable treatment regimen, as judged by the investigator.
Exclusion Criteria:
- Any clinically significant disease or disorder
- Patients with other latent or chronic infections or at risk of infection within 90 days before Visit 2
- An acute exacerbation or acute respiratory infection (upper or lower) requiring oral steroids or antibiotics within 30 days prior to Visit 2
- An FEV1 of <30% of predicted normal at Visit 1
- Patients who have received live or live-attenuated vaccine in the 2 weeks prior to dosing (Visit 2)
- Concomitant diagnosis of significant pulmonary disease other than bronchiectasis or COPD, including symptomatic asthma and allergic bronchopulmonary aspergillosis
- Bronchiectasis associated with a generalised immunodeficiency disorder, where manifestations other than bronchiectasis predominate
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
- Research Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
1
2
Arm Description
Treatment arm AZD5069
Placebo dose.
Outcomes
Primary Outcome Measures
Ratio of Absolute Neutrophil Cell Count in Sputum 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.
Secondary Outcome Measures
Ratio of the Percentage Neutrophil Cell Count in Sputum 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.
Change From Baseline in Weight of 24-hour Sputum Collection
Patients collected all sputum produced during a 24-hour period at baseline and Day 28.
Change From Baseline in Slow Vital Capacity (SVC)
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. SVC is the measure of the change in volume of gas in the lungs from complete inspiration to complete expiration.
Change From Baseline in Forced Vital Capacity (FVC)
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FVC is the maximum volume of air which can be exhaled or inspired during a forced maneuver.
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 is the volume expired in the first second of maximal expiration after a full inspiration.
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEF25-75 is flow rate during the middle half of forced vital capacity (25%-75% of the total volume (FVC) exhaled).
Transition Dyspnea Index (TDI) at End of Treatment (Day 28)
TDI measures changes in dyspnea severity from the baseline as established by the Baseline Dyspnea Index (BDI). TDI is an interviewer-administered rating of severity of dyspnea that assesses Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort domains on a 7-point scale ranging from -3 (major deterioration) to +3 (major improvement). Total score ranges from -9 to +9. The lower the score, the more deterioration in severity of dyspnea.
Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card
The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card
The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, number of puffs of inhalers, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
SGRQ-C 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). The SGRQ-C contains 3 domains:
Symptom (distress due to respiratory symptoms), Activity (disturbance of physical activity) and Impact (overall impact on daily life and well being). All three domains with scale from 0 (best health status) to 100 (worst possible status).
Ratio of Interleukin-1 Beta (IL-1β) in Sputum 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.
Ratio of Interleukin-6 (IL-6) in Sputum 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.
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Sputum 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.
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) in Sputum 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.
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Sputum 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.
Ratio of Growth-related Oncogene-α (GRO-α) in Sputum 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.
Ratio of Interleukin-8 (IL-8) in Sputum 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.
Ratio of Neutrophil Elastase Activity in Sputum 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.
Ratio of Serum Amyloid A (SAA) in Serum 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.
Ratio of C-reactive Protein (CRP) in Serum 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.
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Serum 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.
Ratio of Growth-related Oncogene-α (GRO-α) in Serum 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.
Ratio of Interleukin-6 (IL-6) in Serum 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.
Ratio of Interleukin-1 Beta (IL-1β) in Serum 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.
Ratio of Interleukin-8 (IL-8) in Serum 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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01255592
Brief Title
Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis
Acronym
STRATUS
Official Title
A Phase II Randomised, Double-Blind, Placebo-Controlled, Parallel Group Study to Assess the Efficacy of 28-Day Oral Administration of AZD5069 Twice Daily in Patients With Bronchiectasis
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
February 2012 (Actual)
Study Completion Date
February 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AstraZeneca
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to investigate the effect of AZD5069 in patients with bronchiectasis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bronchiectasis, Lung Disease, Respiratory Diseases
Keywords
Bronchiectasis, Neutrophil, Respiratory disease, Sputum
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
83 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Treatment arm AZD5069
Arm Title
2
Arm Type
Placebo Comparator
Arm Description
Placebo dose.
Intervention Type
Drug
Intervention Name(s)
AZD5069
Intervention Description
Oral dose bid
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Oral dose bid
Primary Outcome Measure Information:
Title
Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Secondary Outcome Measure Information:
Title
Ratio of the Percentage Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Change From Baseline in Weight of 24-hour Sputum Collection
Description
Patients collected all sputum produced during a 24-hour period at baseline and Day 28.
Time Frame
Baseline and end of treatment (Day 28)
Title
Change From Baseline in Slow Vital Capacity (SVC)
Description
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. SVC is the measure of the change in volume of gas in the lungs from complete inspiration to complete expiration.
Time Frame
Baseline to end of treatment (Day 28)
Title
Change From Baseline in Forced Vital Capacity (FVC)
Description
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FVC is the maximum volume of air which can be exhaled or inspired during a forced maneuver.
Time Frame
Baseline to end of treatment (Day 28)
Title
Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
Description
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEV1 is the volume expired in the first second of maximal expiration after a full inspiration.
Time Frame
Baseline to end of treatment (Day 28)
Title
Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)
Description
Lung function tests consisted of 3 forced expiratory maneuvers in which the patient expired forcefully from total lung capacity to residual volume, recorded using a spirometer. FEF25-75 is flow rate during the middle half of forced vital capacity (25%-75% of the total volume (FVC) exhaled).
Time Frame
Baseline to end of treatment (Day 28)
Title
Transition Dyspnea Index (TDI) at End of Treatment (Day 28)
Description
TDI measures changes in dyspnea severity from the baseline as established by the Baseline Dyspnea Index (BDI). TDI is an interviewer-administered rating of severity of dyspnea that assesses Change in Functional Impairment, Change in Magnitude of Task, and Change in Magnitude of Effort domains on a 7-point scale ranging from -3 (major deterioration) to +3 (major improvement). Total score ranges from -9 to +9. The lower the score, the more deterioration in severity of dyspnea.
Time Frame
Baseline to end of treatment (Day 28)
Title
Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card
Description
The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.
Time Frame
Baseline and Last 7 days on treatment
Title
Change From Baseline for the Symptom Scores of the Bronkotest Diary Card
Description
The Bronkotest diary card is a paper based diary card that was filled out by patients daily, recording values from morning and evening peak expiratory flow (PEF) measurements and answering 8 questions on signs and symptoms. Symptom scores were recorded for night-time symptoms, breathing, sputum colour, sputum amount, sputum type, wellbeing, number of puffs of inhalers, and cough, generally scored on a scale from 0 (no symptoms) to 4 (worst symptoms). Summary statistics for baseline (mean of the last 7 days prior to first dose) and change (mean of the last 7 days on treatment - baseline) only contain patients included in the analysis. For symptom scores a decrease is an improvement, for PEF an increase is an improvement.
Time Frame
Baseline and Last 7 days on treatment
Title
Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
Description
SGRQ-C 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). The SGRQ-C contains 3 domains:
Symptom (distress due to respiratory symptoms), Activity (disturbance of physical activity) and Impact (overall impact on daily life and well being). All three domains with scale from 0 (best health status) to 100 (worst possible status).
Time Frame
Baseline and end of treatment (Day 28)
Title
Ratio of Interleukin-1 Beta (IL-1β) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin-6 (IL-6) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Growth-related Oncogene-α (GRO-α) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin-8 (IL-8) in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Neutrophil Elastase Activity in Sputum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Serum Amyloid A (SAA) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of C-reactive Protein (CRP) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Growth-related Oncogene-α (GRO-α) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin-6 (IL-6) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin-1 Beta (IL-1β) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Title
Ratio of Interleukin-8 (IL-8) in Serum at End of Treatment Compared to Baseline
Description
Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.
Time Frame
End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male, or female of non-child bearing potential; ie, women who are permanently or surgically sterilised or post-menopausal.
Aged 18 to 80 years inclusive at screening (Visit 1)
Have a clinical diagnosis of idiopathic or post infective bronchiectasis as diagnosed with a historical high resolution computerised tomography (HRCT) or bronchogram
Be sputum producers with a history of chronic expectoration on most days of most weeks of the year. Patients should have a history of spontaneously producing sputum on a daily basis and should be able to provide at least 2 of the 3 required baseline sputum samples with an average of 3 mL or more.
Be on a stable treatment regimen, as judged by the investigator.
Exclusion Criteria:
Any clinically significant disease or disorder
Patients with other latent or chronic infections or at risk of infection within 90 days before Visit 2
An acute exacerbation or acute respiratory infection (upper or lower) requiring oral steroids or antibiotics within 30 days prior to Visit 2
An FEV1 of <30% of predicted normal at Visit 1
Patients who have received live or live-attenuated vaccine in the 2 weeks prior to dosing (Visit 2)
Concomitant diagnosis of significant pulmonary disease other than bronchiectasis or COPD, including symptomatic asthma and allergic bronchopulmonary aspergillosis
Bronchiectasis associated with a generalised immunodeficiency disorder, where manifestations other than bronchiectasis predominate
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bengt Larsson,, M.B
Organizational Affiliation
AstraZeneca R&D Mölndal
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Ostrava
Country
Czech Republic
Facility Name
Research Site
City
Prague
Country
Czech Republic
Facility Name
Research Site
City
Krakow
Country
Poland
Facility Name
Research Site
City
Lodz
Country
Poland
Facility Name
Research Site
City
Warszawa
Country
Poland
Facility Name
Research Site
City
Hull
State/Province
East Yorkshire
Country
United Kingdom
Facility Name
Research Site
City
Leicester
State/Province
Leicestershire
Country
United Kingdom
Facility Name
Research Site
City
Birmingham
State/Province
Wstmid
Country
United Kingdom
Facility Name
Research Site
City
Belfast
Country
United Kingdom
Facility Name
Research Site
City
Bristol
Country
United Kingdom
Facility Name
Research Site
City
Cambridge
Country
United Kingdom
Facility Name
Research Site
City
London
Country
United Kingdom
Facility Name
Research Site
City
Newcastle-upon-tyne
Country
United Kingdom
Facility Name
Research Site
City
Salford
Country
United Kingdom
Facility Name
Research Site
City
Wolverhampton
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_7111&studyid=209&filename=D3550C00014_Study_Synopsis.pdf
Description
CSR Synopsis
Learn more about this trial
Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis
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