Clinical trial NCT01153321: Investigation of the Effect of Oral Treatment With 100 mg AZD2423 in Subjects With Mild Chronic Obstructive Pulmonary Disease (COPD)
Official title: A Single-Centre, Randomised, Double-Blind, Placebo-Controlled, Parallel Group, Phase IIa Study to Investigate the Effects of 100mg AZD2423 as an Oral Tablet in Subjects With Mild COPD Following Segmental Endobronchial LPS Instillation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Obstructive Pulmonary Disease
Lung Disease
Keywords: Respiratory disease
chronic obstructive pulmonary disease
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2010-06-30
Enrollment: 71
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of the study is to find out if AZD2423 can reduce inflammation in the lungs of patients with mild COPD.


Eligibility criteria: Inclusion Criteria:

* Only women of non-child bearing potential are included in the study i.e. women who are permanently or surgically sterilised or post menopausal.
* ≥ 40 years of age at Visit 1
* Clinical diagnosis of COPD (GOLD stage 1)
* FEV1 ≥ 80% of the predicted normal post-bronchodilator at Visit 1 (GOLD stage 1)
* FEV1/FVC \<70% post-bronchodilator at Visit 1 (GOLD stage 1)

Exclusion Criteria:

* Any clinically significant disease or disorder which, in the opinion of the Investigator, may either put the subject at risk or influence the way the drug works
* Any clinically relevant abnormal findings in physical examination, blood or urine test results, vital signs or ECG at Visit 1 that may put the subject at risk during the study, affect their ability or take part or influence the results of the study
* A past history or current indication of renal (kidney) failure
* Subjects at risk of active tuberculosis or of disease reactivation
* Subjects who have had any clinically significant illness within 4 weeks before Visit 2 (start of treatment)

Primary outcomes:
measure: Absolute Monocyte Count in BAL Post-LPS Challenge
timeFrame: Day 11
Secondary outcomes:
measure: Total Neutrophils in Biopsy Sample (Post-LPS Challenge)
timeFrame: Day 11
measure: Total Macrophages in Biopsy Sample (Post-LPS Challenge)
timeFrame: Day 11
measure: CD45+ in Biopsy Sample (Post-LPS Challenge)
timeFrame: Day 11
measure: CD3+ in Biopsy Sample (Post-LPS Challenge)
timeFrame: Day 11
measure: Biopsy PAS Reaction Grade (Post-LPS Challenge)
timeFrame: Day 11
measure: Biopsy Epithelium Grade (Post-LPS Challenge)
timeFrame: Day 11
measure: Eosinophils in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: Lymphocytes in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: Neutrophils in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: Macrophages in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: TNF α Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: CCL2 Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-1β Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-6 Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-8 Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: RANTES Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: SP-D Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
measure: SAA Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: SAA Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: CCL2 Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: CCL2 Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-1β Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: IL-1β Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-6 Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: IL-6 Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: IL-8 Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: IL-8 Concentration in Blood (Post-LPS Challenge)
timeFrame: day 11
measure: TNF-α Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: TNF-α Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: SP-D Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: SP-D Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: CC16 Concentration in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: CC16 Concentration in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Basophils in Blood (Pre-LPS Challenge)
timeFrame: day 10
measure: Basophils in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Eosinophils in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: Eosinophils in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Lymphocytes in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: Lymphocytes in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Monocytes in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: Monocytes in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Neutrophils in Blood (Pre-LPS Challenge)
timeFrame: Day 10
measure: Neutrophils in Blood (Post-LPS Challenge)
timeFrame: Day 11
measure: Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State
timeFrame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
measure: Time to Cmax (Tmax) of AZD2423 at Steady State
timeFrame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Zero to 24 Hours (AUC(0-24)) of AZD2423 at Steady State
timeFrame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
measure: Area Under the Plasma Concentration-time Curve From Zero to 8 Hours (AUC(0-8)) of AZD2423 at Steady State
timeFrame: Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose
measure: Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes
timeFrame: up to 47 days (visit 1 to visit 6)
measure: Number of Participants With Clinically Relevant Changes in Vital Signs
timeFrame: up to 47 days (visit 1 to visit 6)
measure: Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables
timeFrame: up to 47 days (visit 1 to visit 6)
measure: Number of Participants With Clinically Relevant Changes in Physical Examination
timeFrame: up to 47 days (visit 1 to visit 6)
measure: Number of Participants With Treatment-related or Clinically Relevant Changes in Spirometry (Forced Expiratory Volume in 1 Second [FEV1], Forced Vital Capacity [FVC] Pre-bronchodilator)
timeFrame: up to 47 days (visit 1 to visit 6)
measure: CC16 Concentration in BAL (Post-LPS Challenge)
timeFrame: Day 11
Other outcomes:
Locations:
city: Hannover
country: Germany
facility: Research Site
Study officials:
affiliation: AstraZeneca R&D
name: Bengt Larsson
role: STUDY_DIRECTOR
References: