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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease; Lung Disease
• Intervention / Treatment: Drug: AZD2423; Drug: AZD2423 Placebo

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Oral treatment	Drug: AZD2423; 100mg Oral dose od
Placebo Comparator: 2; Oral treatment	Drug: AZD2423 Placebo; Oral dose od

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Study Director: Bengt Larsson, AstraZeneca R&D

Publications and helpful links

Helpful Links

• D3320C00001 Clinical Study Report Synopsis
• D3320C00001 CSR Synopsis

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: June 28, 2010
• First Submitted That Met QC Criteria: June 29, 2010
• First Posted (Estimate): June 30, 2010

Study Record Updates

• Last Update Posted (Estimate): April 10, 2015
• Last Update Submitted That Met QC Criteria: March 23, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Respiratory disease; chronic obstructive pulmonary disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: D3320C00001; 2010-020141-26 (EudraCT Number)