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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AstraZeneca
ClinicalTrials.gov Identifier:
NCT01255592
First received: December 2, 2010
Last updated: September 7, 2015
Last verified: September 2015
  Purpose
The purpose of this study is to investigate the effect of AZD5069 in patients with bronchiectasis.

Condition Intervention Phase
Bronchiectasis
Lung Disease
Respiratory Diseases
Drug: AZD5069
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Further study details as provided by AstraZeneca:

Primary Outcome Measures:
  • Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and end of treatment (Day 28) ] [ Designated as safety issue: No ]
    Patients collected all sputum produced during a 24-hour period at baseline and Day 28.

  • Change From Baseline in Slow Vital Capacity (SVC) [ Time Frame: Baseline to end of treatment (Day 28) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to end of treatment (Day 28) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to end of treatment (Day 28) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to end of treatment (Day 28) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Baseline to end of treatment (Day 28) ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline and Last 7 days on treatment ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: Baseline and Last 7 days on treatment ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: Baseline and end of treatment (Day 28) ] [ Designated as safety issue: No ]

    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    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 [ Time Frame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits. ] [ Designated as safety issue: No ]
    Ratio of the mean of 3 visits at the end of the treatment period to the mean of the 3 baseline visits.


Enrollment: 83
Study Start Date: February 2011
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Treatment arm AZD5069
Drug: AZD5069
Oral dose bid
Placebo Comparator: 2
Placebo dose.
Drug: Placebo
Oral dose bid

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01255592

Locations
Czech Republic
Research Site
Ostrava, Czech Republic
Research Site
Prague, Czech Republic
Poland
Research Site
Krakow, Poland
Research Site
Lodz, Poland
Research Site
Warszawa, Poland
United Kingdom
Research Site
Hull, East Yorkshire, United Kingdom
Research Site
Leicester, Leicestershire, United Kingdom
Research Site
Birmingham, Wstmid, United Kingdom
Research Site
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
Sponsors and Collaborators
AstraZeneca
Investigators
Study Director: Bengt Larsson,, M.B AstraZeneca R&D Mölndal
  More Information

Additional Information:
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT01255592     History of Changes
Other Study ID Numbers: D3550C00014 
Study First Received: December 2, 2010
Results First Received: June 25, 2015
Last Updated: September 7, 2015
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Czech Republic: State Institute for Drug Control
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by AstraZeneca:
Bronchiectasis
Neutrophil
Respiratory disease
Sputum

Additional relevant MeSH terms:
Bronchiectasis
Lung Diseases
Respiration Disorders
Respiratory Tract Diseases
Bronchial Diseases

ClinicalTrials.gov processed this record on May 03, 2016