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

Phase 2CompletedNCT01153321

AstraZeneca71 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Chronic Obstructive Pulmonary Disease Lung Disease

Interventions

AZD2423DRUG

100mg Oral dose od

AZD2423 PlaceboDRUG

Oral dose od

Eligibility

Sex: ALLMin age: 40 Years

Medical Language ↔ Plain English

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)

Locations (1)

Research Site

Hanover, Hannover, Germany

Outcomes

Primary Outcomes

Absolute Monocyte Count in BAL Post-LPS Challenge

Monocyte count in BAL post-LPS challenge (Day 11)

Time frame: Day 11

Secondary Outcomes

Total Neutrophils in Biopsy Sample (Post-LPS Challenge)

Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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

Data from ClinicalTrials.gov

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Eosinophils in BAL (Post-LPS Challenge)

Post-LPS challenge eosinophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Day 11

SAA Concentration in Blood (Pre-LPS Challenge)

SAA concentration in blood pre-LPS challenge (Day 10).

Time frame: Day 10

SAA Concentration in Blood (Post-LPS Challenge)

SAA concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

CCL2 Concentration in Blood (Pre-LPS Challenge)

CCL2 concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

CCL2 Concentration in Blood (Post-LPS Challenge)

CCL2 concentration in blood post-LPS challenge (Day 11).

Time frame: Day 11

IL-1β Concentration in Blood (Pre-LPS Challenge)

IL-1β concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

IL-1β Concentration in Blood (Post-LPS Challenge)

IL-1β concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

IL-6 Concentration in Blood (Pre-LPS Challenge)

IL-6 concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

IL-6 Concentration in Blood (Post-LPS Challenge)

IL-6 concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

IL-8 Concentration in Blood (Pre-LPS Challenge)

IL-8 concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

IL-8 Concentration in Blood (Post-LPS Challenge)

IL-8 concentration in blood post-LPS challenge (Day 11)

Time frame: day 11

TNF-α Concentration in Blood (Pre-LPS Challenge)

TNF-α concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

TNF-α Concentration in Blood (Post-LPS Challenge)

TNF-α concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

SP-D Concentration in Blood (Pre-LPS Challenge)

SP-D concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

SP-D Concentration in Blood (Post-LPS Challenge)

SP-D concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

CC16 Concentration in Blood (Pre-LPS Challenge)

CC16 concentration in blood pre-LPS challenge (Day 10)

Time frame: Day 10

CC16 Concentration in Blood (Post-LPS Challenge)

CC16 concentration in blood post-LPS challenge (Day 11)

Time frame: Day 11

Basophils in Blood (Pre-LPS Challenge)

Basophils in blood pre-LPS challenge (Day 10)

Time frame: day 10

Basophils in Blood (Post-LPS Challenge)

Basophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Eosinophils in Blood (Pre-LPS Challenge)

Eosinophils in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Eosinophils in Blood (Post-LPS Challenge)

Eosinophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Lymphocytes in Blood (Pre-LPS Challenge)

Lymphocytes in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Lymphocytes in Blood (Post-LPS Challenge)

Lymphocytes in blood post-LPS challenge (Day 11)

Time frame: Day 11

Monocytes in Blood (Pre-LPS Challenge)

Monocytes in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Monocytes in Blood (Post-LPS Challenge)

Monocytes in blood post-LPS challenge (Day 11)

Time frame: Day 11

Neutrophils in Blood (Pre-LPS Challenge)

Neutrophils in blood pre-LPS challenge (Day 10)

Time frame: Day 10

Neutrophils in Blood (Post-LPS Challenge)

Neutrophils in blood post-LPS challenge (Day 11)

Time frame: Day 11

Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State

Steady state pharmacokinetic (PK) profile measured on Day 10

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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