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

Chronic Obstructive Pulmonary Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01153321
• Other study ID #: D3320C00001
• Secondary ID: 2010-020141-26
• Status: Completed
• Phase: Phase 2
• First received: June 28, 2010
• Last updated: March 23, 2015
• Start date: October 2010
• Est. completion date: July 2011

Study information

• Verified date: March 2015
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics CommissionGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chronic Obstructive Pulmonary Disease
• Lung Disease
• Lung Diseases
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive

Intervention

Drug:
• AZD2423
100mg Oral dose od
• AZD2423 Placebo
Oral dose od

Locations

Country	Name	City	State
Germany	Research Site	Hannover

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Monocyte Count in BAL Post-LPS Challenge	Monocyte count in BAL post-LPS challenge (Day 11)	Day 11	No
Secondary	Total Neutrophils in Biopsy Sample (Post-LPS Challenge)	Pre-challenge = Day 11. Biopsies taken from left lingula. Cells counted in subepithelium.	Day 11	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	TNF a Concentration in BAL (Post-LPS Challenge)	Post-LPS challenge TNF a concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.	Day 11	No
Secondary	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	No
Secondary	IL-1ß Concentration in BAL (Post-LPS Challenge)	Post-LPS challenge IL-1ß concentration in BAL (Day 11). LPS challenge and post-LPS challenge BAL conducted at right middle lobe.	Day 11	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	SAA Concentration in Blood (Pre-LPS Challenge)	SAA concentration in blood pre-LPS challenge (Day 10).	Day 10	No
Secondary	SAA Concentration in Blood (Post-LPS Challenge)	SAA concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	CCL2 Concentration in Blood (Pre-LPS Challenge)	CCL2 concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	CCL2 Concentration in Blood (Post-LPS Challenge)	CCL2 concentration in blood post-LPS challenge (Day 11).	Day 11	No
Secondary	IL-1ß Concentration in Blood (Pre-LPS Challenge)	IL-1ß concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	IL-1ß Concentration in Blood (Post-LPS Challenge)	IL-1ß concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	IL-6 Concentration in Blood (Pre-LPS Challenge)	IL-6 concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	IL-6 Concentration in Blood (Post-LPS Challenge)	IL-6 concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	IL-8 Concentration in Blood (Pre-LPS Challenge)	IL-8 concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	IL-8 Concentration in Blood (Post-LPS Challenge)	IL-8 concentration in blood post-LPS challenge (Day 11)	day 11	No
Secondary	TNF-a Concentration in Blood (Pre-LPS Challenge)	TNF-a concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	TNF-a Concentration in Blood (Post-LPS Challenge)	TNF-a concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	SP-D Concentration in Blood (Pre-LPS Challenge)	SP-D concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	SP-D Concentration in Blood (Post-LPS Challenge)	SP-D concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	CC16 Concentration in Blood (Pre-LPS Challenge)	CC16 concentration in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	CC16 Concentration in Blood (Post-LPS Challenge)	CC16 concentration in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	Basophils in Blood (Pre-LPS Challenge)	Basophils in blood pre-LPS challenge (Day 10)	day 10	No
Secondary	Basophils in Blood (Post-LPS Challenge)	Basophils in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	Eosinophils in Blood (Pre-LPS Challenge)	Eosinophils in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	Eosinophils in Blood (Post-LPS Challenge)	Eosinophils in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	Lymphocytes in Blood (Pre-LPS Challenge)	Lymphocytes in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	Lymphocytes in Blood (Post-LPS Challenge)	Lymphocytes in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	Monocytes in Blood (Pre-LPS Challenge)	Monocytes in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	Monocytes in Blood (Post-LPS Challenge)	Monocytes in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	Neutrophils in Blood (Pre-LPS Challenge)	Neutrophils in blood pre-LPS challenge (Day 10)	Day 10	No
Secondary	Neutrophils in Blood (Post-LPS Challenge)	Neutrophils in blood post-LPS challenge (Day 11)	Day 11	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Number of Participants With Clinically Relevant Treatment-related Changes in Laboratory Variables Other Than Monocytes		up to 47 days (visit 1 to visit 6)	No
Secondary	Number of Participants With Clinically Relevant Changes in Vital Signs		up to 47 days (visit 1 to visit 6)	No
Secondary	Number of Participants With Clinically Relevant Changes in Electrocardiogram (ECG) Variables		up to 47 days (visit 1 to visit 6)	No
Secondary	Number of Participants With Clinically Relevant Changes in Physical Examination		up to 47 days (visit 1 to visit 6)	No
Secondary	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)	No
Secondary	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	No

External Links

•   D3320C00001 Clinical Study Report Synopsis
•   D3320C00001 CSR Synopsis