Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis (STRATUS)

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

The purpose of this study is to investigate the effect of AZD5069 in patients with bronchiectasis.

Study Overview

• Status: Completed
• Conditions: Bronchiectasis; Lung Disease; Respiratory Diseases
• Intervention / Treatment: Drug: AZD5069; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• Czech Republic
  • Ostrava, Czech Republic
    • Research Site
  • Prague, Czech Republic
    • Research Site
• Poland
  • Krakow, Poland
    • Research Site
  • Lodz, Poland
    • Research Site
  • Warszawa, Poland
    • Research Site
• United Kingdom
  • Belfast, United Kingdom
    • Research Site
  • Bristol, United Kingdom
    • Research Site
  • Cambridge, United Kingdom
    • Research Site
  • London, United Kingdom
    • Research Site
  • Newcastle-upon-tyne, United Kingdom
    • Research Site
  • Salford, United Kingdom
    • Research Site
  • Wolverhampton, United Kingdom
    • Research Site
  • East Yorkshire
    • Hull, East Yorkshire, United Kingdom
      • Research Site
  • Leicestershire
    • Leicester, Leicestershire, United Kingdom
      • Research Site
  • Wstmid
    • Birmingham, Wstmid, United Kingdom
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 1; Treatment arm AZD5069	Drug: AZD5069; Oral dose bid
PLACEBO_COMPARATOR: 2; Placebo dose.	Drug: Placebo; Oral dose bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	Baseline and end of treatment (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.	Baseline to end of treatment (Day 28)
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.	Baseline to end of treatment (Day 28)
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.	Baseline to end of treatment (Day 28)
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).	Baseline to end of treatment (Day 28)
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.	Baseline to end of treatment (Day 28)
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.	Baseline and Last 7 days on treatment
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.	Baseline and Last 7 days on treatment
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).	Baseline and end of treatment (Day 28)
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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	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) 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.	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) 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 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.	End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Bengt Larsson,, M.B, AstraZeneca R&D Mölndal

Publications and helpful links

Helpful Links

• CSR Synopsis

Study record dates

Study Major Dates

• Study Start: February 1, 2011
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: December 2, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (ESTIMATE): December 7, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): October 8, 2015
• Last Update Submitted That Met QC Criteria: September 7, 2015
• Last Verified: September 1, 2015

More Information

Terms related to this study

• Keywords: Bronchiectasis; Respiratory disease; Neutrophil; Sputum
• Additional Relevant MeSH Terms: Bronchial Diseases; Bronchiectasis; Lung Diseases; Respiration Disorders; Respiratory Tract Diseases
• Other Study ID Numbers: D3550C00014