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

Phase 2

Completed

Conditions: Lung Disease
Chronic Obstructive Pulmonary Disease

Interventions: Drug: AZD2423
Drug: AZD2423 Placebo

Registration Number: NCT01153321

Lead Sponsor: AstraZeneca

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

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 71

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	AZD2423	Oral treatment
2	AZD2423 Placebo	Oral treatment

Primary Outcome Measures

Name	Time	Method
Absolute Monocyte Count in BAL Post-LPS Challenge	Day 11	Monocyte count in BAL post-LPS challenge (Day 11)

Secondary Outcome Measures

Name	Time	Method
Lymphocytes in Blood (Pre-LPS Challenge)	Day 10	Lymphocytes in blood pre-LPS challenge (Day 10)
TNF-α Concentration in Blood (Post-LPS Challenge)	Day 11	TNF-α concentration in blood post-LPS challenge (Day 11)
Neutrophils in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge neutrophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.
CD45+ in Biopsy Sample (Post-LPS Challenge)	Day 11	Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.
CD3+ in Biopsy Sample (Post-LPS Challenge)	Day 11	Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.
Biopsy Epithelium Grade (Post-LPS Challenge)	Day 11	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
SAA Concentration in Blood (Post-LPS Challenge)	Day 11	SAA concentration in blood post-LPS challenge (Day 11)
IL-1β Concentration in Blood (Pre-LPS Challenge)	Day 10	IL-1β concentration in blood pre-LPS challenge (Day 10)
IL-1β Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge IL-1β concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
Total Macrophages in Biopsy Sample (Post-LPS Challenge)	Day 11	Post-LPS challenge data (Day 11). Post-LPS challenge biopsies taken from right middle lobe. Cells counted in subepithelium.
TNF α Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge TNF α concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
CCL2 Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge CCL2 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
SAA Concentration in Blood (Pre-LPS Challenge)	Day 10	SAA concentration in blood pre-LPS challenge (Day 10).
IL-8 Concentration in Blood (Post-LPS Challenge)	day 11	IL-8 concentration in blood post-LPS challenge (Day 11)
TNF-α Concentration in Blood (Pre-LPS Challenge)	Day 10	TNF-α concentration in blood pre-LPS challenge (Day 10)
Total Neutrophils in Biopsy Sample (Post-LPS Challenge)	Day 11	Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.
Biopsy PAS Reaction Grade (Post-LPS Challenge)	Day 11	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).
Eosinophils in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge eosinophil differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.
Lymphocytes in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge lymphocyte differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.
Macrophages in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge macrophage differential in BAL. LPS challenge and post-challenge BAL conducted at right middle lobe.
RANTES Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge RANTES concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
SP-D Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge SP-D concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
SP-D Concentration in Blood (Pre-LPS Challenge)	Day 10	SP-D concentration in blood pre-LPS challenge (Day 10)
Eosinophils in Blood (Post-LPS Challenge)	Day 11	Eosinophils in blood post-LPS challenge (Day 11)
Neutrophils in Blood (Pre-LPS Challenge)	Day 10	Neutrophils in blood pre-LPS challenge (Day 10)
IL-6 Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge IL-6 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
CCL2 Concentration in Blood (Post-LPS Challenge)	Day 11	CCL2 concentration in blood post-LPS challenge (Day 11).
CC16 Concentration in Blood (Post-LPS Challenge)	Day 11	CC16 concentration in blood post-LPS challenge (Day 11)
Basophils in Blood (Pre-LPS Challenge)	day 10	Basophils in blood pre-LPS challenge (Day 10)
Neutrophils in Blood (Post-LPS Challenge)	Day 11	Neutrophils in blood post-LPS challenge (Day 11)
Maximum Plasma Concentration (Cmax) of AZD2423 at Steady State	Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose	Steady state pharmacokinetic (PK) profile measured on Day 10
Time to Cmax (Tmax) of AZD2423 at Steady State	Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose	Steady state PK profile measured on Day 10
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)	Day 11	Post-LPS challenge CC16 concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
IL-8 Concentration in BAL (Post-LPS Challenge)	Day 11	Post-LPS challenge IL 8 concentration in BAL. LPS challenge and post-LPS challenge BAL conducted at right middle lobe.
CCL2 Concentration in Blood (Pre-LPS Challenge)	Day 10	CCL2 concentration in blood pre-LPS challenge (Day 10)
IL-1β Concentration in Blood (Post-LPS Challenge)	Day 11	IL-1β concentration in blood post-LPS challenge (Day 11)
IL-6 Concentration in Blood (Pre-LPS Challenge)	Day 10	IL-6 concentration in blood pre-LPS challenge (Day 10)
IL-6 Concentration in Blood (Post-LPS Challenge)	Day 11	IL-6 concentration in blood post-LPS challenge (Day 11)
SP-D Concentration in Blood (Post-LPS Challenge)	Day 11	SP-D concentration in blood post-LPS challenge (Day 11)
Basophils in Blood (Post-LPS Challenge)	Day 11	Basophils in blood post-LPS challenge (Day 11)
Monocytes in Blood (Pre-LPS Challenge)	Day 10	Monocytes in blood pre-LPS challenge (Day 10)
Monocytes in Blood (Post-LPS Challenge)	Day 11	Monocytes in blood post-LPS challenge (Day 11)
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 Physical Examination	up to 47 days (visit 1 to visit 6)
IL-8 Concentration in Blood (Pre-LPS Challenge)	Day 10	IL-8 concentration in blood pre-LPS challenge (Day 10)
Eosinophils in Blood (Pre-LPS Challenge)	Day 10	Eosinophils in blood pre-LPS challenge (Day 10)
Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables	up to 47 days (visit 1 to visit 6)
CC16 Concentration in Blood (Pre-LPS Challenge)	Day 10	CC16 concentration in blood pre-LPS challenge (Day 10)
Lymphocytes in Blood (Post-LPS Challenge)	Day 11	Lymphocytes in blood post-LPS challenge (Day 11)
Area Under the Plasma Concentration-time Curve From Zero to 24 Hours (AUC(0-24)) of AZD2423 at Steady State	Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose	Steady state PK profile measured on Day 10
Area Under the Plasma Concentration-time Curve From Zero to 8 Hours (AUC(0-8)) of AZD2423 at Steady State	Day 10 pre-dose, 20 and 40 minutes post-dose, 1, 1.5, 2, 3, 4, 6 and 8 hours post-dose	Steady state PK profile measured on Day 10