Investigation of the Effect of Oral Treatment With 100 mg AZD2423 in Subjects With Mild Chronic Obstructive Pulmonary Disease (COPD)

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

Official Title
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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

Conditions
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Chronic Obstructive Pulmonary Disease, Lung Disease

Intervention / Treatment
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* Drug: AZD2423
* Drug: AZD2423 Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Oral treatment | Drug: AZD2423<br>* 100mg Oral dose od<br>|
| Placebo Comparator: 2<br>Oral treatment | Drug: AZD2423 Placebo<br>* Oral dose od<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Monocyte Count in BAL Post-LPS Challenge | Monocyte count in BAL post-LPS challenge (Day 11) | Day 11 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Neutrophils in Biopsy Sample (Post-LPS Challenge) | Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium. | Day 11 | 
| Total Macrophages in Biopsy Sample (Post-LPS Challenge) | Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium. | Day 11 | 
| CD45+ in Biopsy Sample (Post-LPS Challenge) | Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium. | Day 11 | 
| CD3+ in Biopsy Sample (Post-LPS Challenge) | Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium. | Day 11 | 
| Biopsy PAS Reaction Grade (Post-LPS Challenge) | Biopsies stained using PAS method. Graded on subjective scale (1=normal; 2=PAS positive cell hypertrophy; 3=PAS positive cell hyperplasia; 4=Metaplasia with PAS positive cells throughout mucosa; 5=Metaplasia and/or squamous plates with loss of PAS positive cells). | Day 11 | 
| Biopsy Epithelium Grade (Post-LPS Challenge) | Biopsies (from right middle lobe) were assessed for routine histopathology. Epithelial morphology was graded on subjective scale from 1 to 5. 1=normal; 2=PAS positive cell hypertrophy; 3=PAS positive cell hyperplasia; 4=Metaplasia with PAS positive cells throughout mucosa; 5=Metaplasia and/or squamous plates with loss of PAS positive cells | Day 11 | 
| Eosinophils in BAL (Post-LPS Challenge) | Post-LPS challenge eosinophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe. | Day 11 | 
| Lymphocytes in BAL (Post-LPS Challenge) | Post-LPS challenge lymphocyte differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe. | Day 11 | 
| Neutrophils in BAL (Post-LPS Challenge) | Post-LPS challenge neutrophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe. | Day 11 | 
| Macrophages in BAL (Post-LPS Challenge) | Post-LPS challenge macrophage differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe. | Day 11 | 
| TNF α Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge TNF α concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| CCL2 Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge CCL2 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| IL-1β Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge IL-1β concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| IL-6 Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge IL-6 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| IL-8 Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge IL 8 concentration in BAL. LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| RANTES Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge RANTES concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| SP-D Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge SP-D concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 
| SAA Concentration in Blood (Pre-LPS Challenge) | SAA concentration in blood pre-LPS challenge (Day 10). | Day 10 | 
| SAA Concentration in Blood (Post-LPS Challenge) | SAA concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| CCL2 Concentration in Blood (Pre-LPS Challenge) | CCL2 concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| CCL2 Concentration in Blood (Post-LPS Challenge) | CCL2 concentration in blood post-LPS challenge (Day 11). | Day 11 | 
| IL-1β Concentration in Blood (Pre-LPS Challenge) | IL-1β concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| IL-1β Concentration in Blood (Post-LPS Challenge) | IL-1β concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| IL-6 Concentration in Blood (Pre-LPS Challenge) | IL-6 concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| IL-6 Concentration in Blood (Post-LPS Challenge) | IL-6 concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| IL-8 Concentration in Blood (Pre-LPS Challenge) | IL-8 concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| IL-8 Concentration in Blood (Post-LPS Challenge) | IL-8 concentration in blood post-LPS challenge (Day 11) | day 11 | 
| TNF-α Concentration in Blood (Pre-LPS Challenge) | TNF-α concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| TNF-α Concentration in Blood (Post-LPS Challenge) | TNF-α concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| SP-D Concentration in Blood (Pre-LPS Challenge) | SP-D concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| SP-D Concentration in Blood (Post-LPS Challenge) | SP-D concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| CC16 Concentration in Blood (Pre-LPS Challenge) | CC16 concentration in blood pre-LPS challenge (Day 10) | Day 10 | 
| CC16 Concentration in Blood (Post-LPS Challenge) | CC16 concentration in blood post-LPS challenge (Day 11) | Day 11 | 
| Basophils in Blood (Pre-LPS Challenge) | Basophils in blood pre-LPS challenge (Day 10) | day 10 | 
| Basophils in Blood (Post-LPS Challenge) | Basophils in blood post-LPS challenge (Day 11) | Day 11 | 
| Eosinophils in Blood (Pre-LPS Challenge) | Eosinophils in blood pre-LPS challenge (Day 10) | Day 10 | 
| Eosinophils in Blood (Post-LPS Challenge) | Eosinophils in blood post-LPS challenge (Day 11) | Day 11 | 
| Lymphocytes in Blood (Pre-LPS Challenge) | Lymphocytes in blood pre-LPS challenge (Day 10) | Day 10 | 
| Lymphocytes in Blood (Post-LPS Challenge) | Lymphocytes in blood post-LPS challenge (Day 11) | Day 11 | 
| Monocytes in Blood (Pre-LPS Challenge) | Monocytes in blood pre-LPS challenge (Day 10) | Day 10 | 
| Monocytes in Blood (Post-LPS Challenge) | Monocytes in blood post-LPS challenge (Day 11) | Day 11 | 
| Neutrophils in Blood (Pre-LPS Challenge) | Neutrophils in blood pre-LPS challenge (Day 10) | Day 10 | 
| Neutrophils in Blood (Post-LPS Challenge) | Neutrophils in blood post-LPS challenge (Day 11) | Day 11 | 
| Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State | Steady state pharmacokinetic (PK) profile measured on Day 10 | Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose | 
| Time to Cmax (Tmax) of AZD2423 at Steady State | Steady state PK profile measured on Day 10 | Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose | 
| Area Under the Plasma Concentration-time Curve From Zero to 24 Hours (AUC(0-24)) of AZD2423 at Steady State | Steady state PK profile measured on Day 10 | Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose | 
| Area Under the Plasma Concentration-time Curve From Zero to 8 Hours (AUC(0-8)) of AZD2423 at Steady State | Steady state PK profile measured on Day 10 | Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose | 
| Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes |  | up to 47 days (visit 1 to visit 6) | 
| Number of Participants With Clinically Relevant Changes in Vital Signs |  | up to 47 days (visit 1 to visit 6) | 
| Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables |  | up to 47 days (visit 1 to visit 6) | 
| Number of Participants With Clinically Relevant Changes in Physical Examination |  | up to 47 days (visit 1 to visit 6) | 
| 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) |  | up to 47 days (visit 1 to visit 6) | 
| CC16 Concentration in BAL (Post-LPS Challenge) | Post-LPS challenge CC16 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe. | Day 11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory disease, chronic obstructive pulmonary disease