Clinical trial NCT01255592: Evaluation of the Effect of AZD5069 in Patients With Bronchiectasis
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Bronchiectasis
Lung Disease
Respiratory Diseases
Keywords: Bronchiectasis
Neutrophil
Respiratory disease
Sputum
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-12-07
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Ratio of Absolute Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Secondary outcomes:
measure: Ratio of the Percentage Neutrophil Cell Count in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Change From Baseline in Weight of 24-hour Sputum Collection
timeFrame: Baseline and end of treatment (Day 28)
measure: Change From Baseline in Slow Vital Capacity (SVC)
timeFrame: Baseline to end of treatment (Day 28)
measure: Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline to end of treatment (Day 28)
measure: Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline to end of treatment (Day 28)
measure: Change From Baseline in Forced Expiratory Flow Between 25% and 75% of Forced Vital Capacity (FEF25-75)
timeFrame: Baseline to end of treatment (Day 28)
measure: Transition Dyspnea Index (TDI) at End of Treatment (Day 28)
timeFrame: Baseline to end of treatment (Day 28)
measure: Change From Baseline for the Morning PEF and Evening PEF of the Bronkotest Diary Card
timeFrame: Baseline and Last 7 days on treatment
measure: Change From Baseline for the Symptom Scores of the Bronkotest Diary Card
timeFrame: Baseline and Last 7 days on treatment
measure: Change From Baseline Total and Domain Scores in St. George's Respiratory Questionnaire for COPD Patients (SGRQ-C)
timeFrame: Baseline and end of treatment (Day 28)
measure: Ratio of Interleukin-1 Beta (IL-1β) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Interleukin-6 (IL-6) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Regulated on Activation, Normal T Cell Expressed and Secreted (RANTES) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Monocyte Chemoattractant Protein-1 (MCP-1) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Growth-related Oncogene-α (GRO-α) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Interleukin-8 (IL-8) in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Neutrophil Elastase Activity in Sputum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Serum Amyloid A (SAA) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of C-reactive Protein (CRP) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Tumor Necrosis Factor Alpha (TNF-α) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Growth-related Oncogene-α (GRO-α) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Interleukin-6 (IL-6) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Interleukin-1 Beta (IL-1β) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
measure: Ratio of Interleukin-8 (IL-8) in Serum at End of Treatment Compared to Baseline
timeFrame: End of treatment values from 3 visits (day 21 to 28) and baseline values from 3 visits.
Other outcomes:
Locations:
city: Ostrava
country: Czech Republic
facility: Research Site
city: Prague
country: Czech Republic
facility: Research Site
city: Krakow
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Hull
country: United Kingdom
facility: Research Site
state: East Yorkshire
city: Leicester
country: United Kingdom
facility: Research Site
state: Leicestershire
city: Birmingham
country: United Kingdom
facility: Research Site
state: Wstmid
city: Belfast
country: United Kingdom
facility: Research Site
city: Bristol
country: United Kingdom
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle-upon-tyne
country: United Kingdom
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
city: Wolverhampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D Mölndal
name: Bengt Larsson,, M.B
role: STUDY_DIRECTOR
References: