Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis

Bronchiectasis Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01255592
• Other study ID #: D3550C00014
• Status: Completed
• Phase: Phase 2
• First received: December 2, 2010
• Last updated: September 7, 2015
• Start date: February 2011
• Est. completion date: February 2012

Study information

• Verified date: September 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyCzech Republic: State Institute for Drug ControlPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 83
• Est. completion date: February 2012
• Est. primary completion date: February 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

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

Related Conditions & MeSH terms

• Bronchiectasis
• Lung Disease
• Lung Diseases
• Respiration Disorders
• Respiratory Diseases
• Respiratory Tract Diseases

Intervention

Drug:
• AZD5069
Oral dose bid
• Placebo
Oral dose bid

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

Czech Republic,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	No
Secondary	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.	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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	Yes
Secondary	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	Yes
Secondary	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)	No
Secondary	Ratio of Interleukin-1 Beta (IL-1ß) 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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Ratio of Tumor Necrosis Factor Alpha (TNF-a) 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.	No
Secondary	Ratio of Growth-related Oncogene-a (GRO-a) 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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	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.	No
Secondary	Ratio of Tumor Necrosis Factor Alpha (TNF-a) 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.	No
Secondary	Ratio of Growth-related Oncogene-a (GRO-a) 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.	No
Secondary	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.	No
Secondary	Ratio of Interleukin-1 Beta (IL-1ß) 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.	No
Secondary	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.	No

External Links

•   CSR Synopsis